Proteomic Analysis of Postoperative Delirium from a randomized trial in Older Patients undergoing Cardiac Surgery exposed to Intraoperative Normoxia versus Hyperoxia: A Nested Case-Control Study

接受心脏手术的老年患者术中常氧与高氧的随机试验对术后谵妄的蛋白质组学分析：巢式病例对照研究

• 批准号: 9751173
• 负责人: Shahzad Shaefi
• 金额: $ 13.13万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751173
• 关键词: Acute; Adult; Affect; Age-Years; Aging; Biological; Biological Markers; Blood; Blood specimen; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cognitive; Confusion; Coronary Artery Bypass; Country; Data; Delirium; Dependence; Development; Diagnosis; Disease; Elderly; Exposure to; Functional disorder; Hospitals; Human; Hyperoxia; Impaired cognition; Incidence; Inflammation; Inflammatory; Inflammatory Response; Length; Length of Stay; Link; Measures; Modeling; Morbidity - disease rate; Nested Case-Control Study; Neurocognition; Operative Surgical Procedures; Organ; Outcome; Oxygen; Pathway interactions; Patients; Perioperative; Phase; Plasma; Population; Postoperative Period; Prevention approach; Prevention strategy; Proteins; Proteomics; Public Health; Randomized; Randomized Controlled Trials; Reperfusion Injury; Role; Sampling; Serum; Syndrome; Time; Ventilator; biomarker discovery; case control; cohort; control trial; cost; cytokine; design; experience; human old age (65+); improved; mortality; novel; older patient; oxidative damage; postoperative delirium; prevent; prospective; protein biomarkers; public health relevance; randomized trial; response; treatment strategy

Abstract Delirium following cardiac surgery affects approximately 30-50% of patients, totaling 200,000 patients per year in this country alone, with patients over 70 years of age representing roughly 50% of those undergoing cardiac surgery. Perioperative delirium in the elderly cardiac surgical patient confers a significant morbid burden of poor functional and cognitive outcome, increased hospital length of stay and increased mortality. The public health impact of delirium in this population will likely only increase over time, making the development of effective approaches to prevention and treatment even more imperative. Further, there are accumulating data that oxidative damage and inflammatory response during cardiopulmonary bypass (CPB) contributes to postoperative organ dysfunction. Additionally, end organ dysfunction, morbidity and mortality have been linked to the deleterious effects of hyperoxia following ischemia-reperfusion injuries in several other disease states. In the current proposal we aim to leverage stored plasma samples collected as part of a prospective randomized controlled trial of patients randomized to one of two intraoperative ventilator management strategies in which the fraction of inspired oxygen is titrated to hyperoxia (100%) or normoxia (35%) conditions with corresponding blood oxygen levels, in order to undertake a nested, case control study. In this factorial design we will establish four matched cohorts of delirium positive, delirium negative, hyperoxia exposed and normoxia exposed patient samples and will apply state-of-the-art approaches, including advanced proteomics, to assess circulating proteins with a view towards biomarker discovery. Specifically, we aim to quantitatively assess the relationship between plasma inflammatory biomarker load with delirium and intraoperative hyperoxia, using advanced proteomic analysis, sampled at two intraoperative time points before and after CPB among patients 65 years old and over undergoing CABG surgery. Using this model we will seek to further elucidate the pathophysiological model related to delirium and hyperoxia, with the hope of identifying novel serum biomarkers that may be predictive of, interact with, or define delirium signatures. Results of the proposed analyses will provide the basis for further mechanistic studies to inform the development of prevention and treatment strategies for postoperative delirium in cardiac surgery and used to lessen the harmful impact of delirium in aging adults.

抽象的 心脏手术后谵妄影响大约 30-50% 的患者，总计 200,000 人 仅在这个国家每年就有 70 岁以上的患者，其中 70 岁以上的患者大约占 50%的人接受心脏手术。老年心脏手术围术期谵妄 患者承担了功能和认知结果不佳的显着病态负担，增加了 住院时间和死亡率增加。谵妄对公共卫生的影响 随着时间的推移，人口可能只会增加，因此需要制定有效的方法 预防和治疗更是刻不容缓。此外，还有越来越多的数据表明 体外循环（CPB）期间的氧化损伤和炎症反应有助于 导致术后器官功能障碍。此外，终末器官功能障碍、发病率和死亡率 与缺血再灌注损伤后高氧的有害影响有关 在其他几种疾病状态中。在当前的提案中，我们的目标是利用储存的血浆 作为前瞻性随机对照试验的一部分收集的样本，患者被随机分配到 两种术中呼吸机管理策略之一，其中吸入的部分 用相应的血液将氧气滴定至高氧（100%）或常氧（35%）条件 氧水平，以便进行巢式病例对照研究。在这个因子设计中，我们将 建立四个匹配的谵妄阳性、谵妄阴性、高氧暴露和 含氧量正常的患者样本，并将采用最先进的方法，包括 先进的蛋白质组学，评估循环蛋白质，以发现生物标志物。 具体来说，我们的目标是定量评估血浆炎症之间的关系 使用先进的蛋白质组学分析，进行谵妄和术中高氧的生物标志物负荷， 在 65 岁患者的 CPB 前后两个术中时间点采样 并接受冠状动脉搭桥手术。使用这个模型，我们将寻求进一步阐明 与谵妄和高氧血症相关的病理生理模型，希望能够识别新的 可以预测谵妄特征、与谵妄特征相互作用或定义谵妄特征的血清生物标志物。结果 拟议的分析将为进一步的机制研究提供基础，以告知 心脏手术术后谵妄防治策略的制定 并用于减轻老年人谵妄的有害影响。