Role of Blood–Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2023-08-24 DOI:10.1002/ana.26771

Michael J. Devinney MD, PhD, Megan K. Wong MD, Mary Cooter Wright MS, Edward R. Marcantonio MD, SM, Niccolò Terrando PhD, Jeffrey N. Browndyke PhD, Heather E. Whitson MD, MHS, Harvey J. Cohen MD, Andrea G. Nackley PhD, Marguerita E. Klein BS, E. Wesley Ely MD, MPH, Joseph P. Mathew MD, MHSc, MBA, Miles Berger MD, PhD, for the MADCO-PC and INTUIT Study Teams

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引用次数: 1

Abstract

Objective

Although animal models suggest a role for blood–brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood–brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.

Methods

Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood–brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).

Results

Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = −0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [−0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03–1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09–1.22, p < 0.001).

Interpretation

Postoperative increases in blood–brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood–brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024–1035

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血脑屏障功能障碍在老年人非心脏手术后谵妄中的作用。

目的：尽管动物模型表明血脑屏障功能障碍在术后谵妄样行为中的作用，但其在人类术后谵语和术后恢复中的作用尚不清楚。因此，我们评估了血脑屏障功能障碍在老年手术患者术后谵妄和住院时间中的作用。方法：前瞻性地在非心脏、非神经手术前后进行认知测试、谵妄评估、脑脊液和血液采样。使用脑脊液与血浆白蛋白比率（CPAR）评估血脑屏障功能障碍。结果：207名患者（中位年龄 = 68 年，45%女性），有完整的CPAR和谵妄数据，26例（12.6%）发生术后谵妄。总体而言，CPAR从之前增加到24 手术后数小时（中位数变化 = 0.28，四分位间距[IQR]=-0.48至1.24，Wilcoxon p = 0.001）。术前至24 发生谵妄的患者术后数小时CPAR的变化大于未发生谵妄患者（中位数[IQR]= 1.31[0.004至2.34]vs 0.19[0.55至1.08]，p = 0.003）。在一个调整了年龄、基线认知和手术类型的多变量模型中，术前至24 CPAR术后数小时的变化与谵妄的发生独立相关（每次CPAR增加1，比值比 = 1.30，95%置信区间[CI]= 1.03-1.63，p = 0.026）和住院时间增加（发病率比率 = 1.15，95%CI = 1.09-1.22，第页解释：术后血脑屏障通透性的增加与谵妄发生率和术后住院时间的增加独立相关。尽管这些发现没有建立因果关系，但有必要进行研究，以确定减少术后血脑屏障功能障碍的干预措施是否会降低术后谵妄发生率和住院时间。ANN NEUROL 2023。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.