Cerebral Autoregulation in the Cardiac Surgery Intensive Care Unit: Associations with Postoperative Delirium, Cognitive Change, and Biomarkers of Brain Injury

心脏手术重症监护病房中的大脑自动调节：与术后谵妄、认知变化和脑损伤生物标志物的关联

• 批准号: 10209372
• 负责人: Charles Hugh Brown
• 金额: $ 121.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10209372
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Alzheimer' s disease related dementia; Biological Markers; Blood; Blood Pressure; Brain; Brain Injuries; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Characteristics; Cognitive; Coupled; Data; Delirium; Enrollment; Ensure; Event; Future; Goals; High Prevalence; Homeostasis; Hour; Impaired cognition; Impairment; Inflammation; Intensive Care Units; Ischemia; Lead; Measurement; Measures; Mediating; Memory; Methods; Monitor; Nerve Degeneration; Neuronal Injury; Neuropsychology; Observational Study; Operating Rooms; Operative Surgical Procedures; Patients; Perfusion; Perioperative; Pharmaceutical Preparations; Phase; Pilot Projects; Postoperative Complications; Postoperative Period; Process; Research; Risk; Risk Factors; Role; Stroke; Variant; Work; base; blood pressure regulation; cerebrovascular; cognitive change; cohort; follow-up; improved; individual patient; insight; modifiable risk; novel; organ injury; patient subsets; population based; postoperative delirium; pressure; prevent; randomized trial; tau Proteins; treatment arm; treatment as usual

PROJECT SUMMARY/ABSTRACT Delirium occurs in up to 50% of patients after cardiac surgery and is associated with cognitive decline and Alzheimer’s disease and related dementias (ADRD). However, the underlying mechanisms for these complications are elusive. Further, the extent to which events in the early postoperative period increase risk for delirium, cognitive decline, and ADRD is unclear. The goal of this proposal is to examine cerebrovascular contributions to delirium / cognitive decline, with a focus on cerebral perfusion in the cardiac surgery intensive care unit (ICU). Given the wide variations in blood pressure in the ICU, coupled with the high prevalence of cerebrovascular disease, cerebral malperfusion in the ICU may contribute to delirium and cognitive decline. Current practice of targeting empiric mean arterial pressure (MAP) goals in the perioperative period may be inadequate for individual patients. Our group has championed a more personalized method based on cerebral autoregulation monitoring. Through the process of cerebral autoregulation, the brain is regulated to maintain a constant cerebral blood flow across a range of MAP. However, when MAP exceeds limits of autoregulation or when autoregulation is impaired, compensatory mechanisms fail and inadequate or excessive cerebral blood flow results. Our work in the cardiac surgery operating room has shown several results that emphasize the importance of individualizing blood pressure goals. First, the MAPs at the limits of autoregulation vary widely in patients, and both impaired autoregulation and MAP outside the limits of autoregulation are associated with organ injury. Second, in a recent trial, targeting MAP to be >lower limit of autoregulation during cardio- pulmonary bypass vs. usual care reduced delirium by 28% and improved memory scores at 1- and 12-months. To date, the majority of research has been conducted in the operating room during cardiopulmonary bypass. However, our preliminary data suggests that the early phase of ICU care may be equally important. In a small pilot study, we found that in the ICU, the extent of MAP outside the limits of autoregulation, as well as impaired autoregulation, were associated with delirium. Importantly, cognitive change was not assessed in this pilot and mechanisms for these findings are unclear. These results motivate the proposed observational study, which will examine whether (a) MAP outside the limits of autoregulation and (b) impaired autoregulation in the ICU are associated with delirium after cardiac surgery (Aim 1) and cognitive change from baseline at 1- and 12- months (Aim 2). In an exploratory mechanistic aim (Aim 3), we will characterize whether perioperative brain injury mediates or baseline neurodegeneration moderates the association of cerebral autoregulation characteristics and delirium and cognitive decline. The results of this study will more precisely characterize the role of cerebral malperfusion in the ICU with delirium and will identify mechanisms through which brain injury occurs. Promising results would also support a trial to target MAP in the ICU based on these methods. Although the cohort is only followed for one year, these results may also provide insight into potential mechanisms for longer-term cognitive decline and ADRD.

项目总结/摘要 多达50%的患者在心脏手术后发生谵妄，并与认知能力下降和 阿尔茨海默病和相关痴呆症（ADRD）。然而，这些潜在机制 并发症是难以捉摸的。此外，术后早期事件增加风险的程度 谵妄认知能力下降和ADRD的治疗尚不清楚这项建议的目的是检查脑血管 导致谵妄/认知能力下降，重点关注心脏手术中的脑灌注 监护病房（ICU）。鉴于ICU中血压的广泛变化，加上高患病率， 脑血管疾病，ICU中的脑灌注不良可能导致谵妄和认知能力下降。 目前在围手术期以经验性平均动脉压（MAP）为目标的做法可能是 不适合个别患者。我们的团队倡导一种基于大脑的更个性化的方法， 自动调节监测通过大脑的自动调节过程，大脑被调节以维持一个 在MAP范围内保持恒定的脑血流量。然而，当MAP超过自动调节的极限或 当自动调节受损时，代偿机制失效， 流量结果。我们在心脏外科手术室的工作显示了几个结果，强调了 个体化血压目标的重要性。首先，在自动调节极限的MAP变化很大 在患者中，受损的自动调节和MAP超出自动调节范围与 器官损伤其次，在最近的一项试验中，将MAP定为>心脏手术期间自动调节的下限， 与常规护理相比，肺分流术减少了28%的谵妄，并改善了1个月和12个月的记忆评分。 到目前为止，大多数研究都是在心肺转流手术室中进行的。 然而，我们的初步数据表明，早期ICU护理可能同样重要。在一个小 初步研究，我们发现，在ICU，MAP的范围外的自我调节，以及受损 自动调节，与谵妄有关。重要的是，在该试验中没有评估认知变化， 这些发现的机制尚不清楚。这些结果激发了拟议的观察性研究， 将检查ICU中是否存在（a）MAP超出自动调节限度和（B）自动调节受损 与心脏手术后谵妄（目标1）和1- 12- 14岁时较基线的认知变化相关。 月（目标2）。在探索性机制目标（目标3）中，我们将描述围手术期脑 损伤介导或基线神经退行性变缓和脑自动调节的关联 精神错乱和认知能力下降。 这项研究的结果将更准确地描述脑灌注不良在ICU中的作用， 谵妄，并将确定脑损伤发生的机制。有希望的结果也将支持 一项基于这些方法的针对ICU MAP的试验。虽然该队列仅随访一年， 这些结果也可能为长期认知能力下降和ADRD的潜在机制提供见解。