Devinney Michael J, Wong Megan K, Wright Mary Cooter, Marcantonio Edward R, Terrando Niccolò, Browndyke Jeffrey N, Whitson Heather E, Cohen Harvey J, Nackley Andrea G, Klein Marguerita E, Ely E Wesley, Mathew Joseph P, Berger Miles
Department of Anesthesiology, Duke University School of Medicine, Durham NC.
Duke Center for the Study of Aging and Human Development, Duke University Medical Center, Durham NC.
medRxiv. 2023 May 10:2023.04.07.23288303. doi: 10.1101/2023.04.07.23288303.
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.
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).
Of 207 patients (median age 68, 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 postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 1.15 [95% CI 1.09-1.22]; p<0.001).
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.
尽管动物模型提示血脑屏障功能障碍在术后谵妄样行为中起作用，但其在人类术后谵妄及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及住院时间方面的作用。
在非心脏、非神经外科手术前后，前瞻性地进行认知测试、谵妄评估以及脑脊液和血液采样。使用脑脊液与血浆白蛋白比率（CPAR）评估血脑屏障功能障碍。
在207例有完整CPAR和谵妄数据的患者（中位年龄68岁，45%为女性）中，26例（12.6%）发生了术后谵妄。总体而言，CPAR从术前到术后24小时有所增加（术后中位变化0.28，[四分位间距][-0.48 - 1.24]；Wilcoxon检验p = 0.001）。发生谵妄的患者术前至术后24小时CPAR的变化大于未发生谵妄的患者（中位[四分位间距]1.31 [0.004, 2.34]对0.19 [-0.55, 1.08]；p = 0.003）。在调整年龄、基线认知和手术类型的多变量模型中，术前至术后24小时CPAR的变化与谵妄发生率独立相关（CPAR每增加1，比值比=1.30，[95%置信区间1.03 - 1.63]；p = 0.026）以及住院时间延长相关（发病率比值比=1.15 [95%置信区间1.09 - 1.22]；p < 0.001）。
术后血脑屏障通透性增加与谵妄发生率增加及术后住院时间延长独立相关。尽管这些发现未确立因果关系，但有必要开展研究以确定降低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。
