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

项目摘要/摘要 高达50%的心脏手术后患者会出现妄想，并与认知能力下降和 阿尔茨海默病和相关痴呆(ADRD)。然而，这些问题的基本机制 并发症是难以捉摸的。此外，术后早期发生的事件增加风险的程度 对于精神错乱、认知能力下降和ADRD，目前还不清楚。这项建议的目标是检查脑血管 心内直视手术患者脑血流灌注对精神障碍/认知功能下降的影响 监护室(ICU)。鉴于ICU的血压变化很大，再加上高血压的高患病率 ICU中的脑血管疾病、脑灌注不良可能导致神志不清和认知能力下降。 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 不适用于个别患者。我们团队倡导了一种基于大脑的更个性化的方法 自动调节监控。通过大脑的自动调节过程，大脑被调节以维持 在一系列MAP中持续的脑血流量。但是，当MAP超过自动调节限制或 当自我调节受损时，代偿机制失效，脑血不足或过多 流动结果。我们在心脏外科手术室的工作显示了几个结果，强调了 个性化血压目标的重要性。首先，自动监管极限的地图差别很大。 在患者中，自我调节受损和自我调节范围之外的MAP都与 器官损伤。第二，在最近的一项试验中，将MAP定为有氧运动中自动调节的下限。 与常规护理相比，肺搭桥术减少了28%的精神错乱，并在1个月和12个月时改善了记忆评分。 到目前为止，大多数研究都是在体外循环期间在手术室进行的。 然而，我们的初步数据表明，ICU护理的早期阶段可能同样重要。在一个小的 前期研究发现，在ICU中，MAP的范围超出了自动调节的范围，以及受损 自我调节与精神错乱有关。重要的是，在这项试验中没有评估认知变化， 这些发现的机制尚不清楚。这些结果推动了拟议的观察性研究，该研究 将检查(A)MAP是否超出自动调节的限制和(B)ICU中的自动调节受损 与心脏手术后精神错乱(目标1)和1-和12-基线的认知变化有关 月(目标2)。在探索性机械目标(目标3)中，我们将描述围手术期大脑 损伤介导或基线神经退行性改变缓和脑自身调节的联系 特点及神志不清和认知功能衰退。 这项研究的结果将更准确地描述脑灌注不良在重症监护病房中的作用 并将确定脑损伤发生的机制。令人振奋的结果也将支持 基于这些方法在ICU靶向MAP的尝试。虽然这个队列只被跟踪了一年， 这些结果也可能为长期认知衰退和ADRD的潜在机制提供洞察力。

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.