Payne Thomas, Taylor Jennifer, Kunkel David, Konieczka Katherine, Ingram Frankie, Blennow Kaj, Zetterberg Henrik, Pearce Robert A, Meyer-Franke Anke, Terrando Niccolò, Akassoglou Katerina, Sanders Robert D, Lennertz Richard C
Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia.
BJA Open. 2024 Oct 5;12:100349. doi: 10.1016/j.bjao.2024.100349. eCollection 2024 Dec.
We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity.
We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair. CSF samples were obtained before (=24) and after surgery (=13), with some participants having multiple postoperative samples. Our primary outcome was the perioperative change in CSF fibrinogen. Delirium was assessed using the Delirium Rating Scale-Revised-98.
CSF fibrinogen increased after surgery (<0.001), and this was associated with an increase in CSF/plasma albumin ratio (β=1.09, 95% CI 0.47-1.71, =0.004). The peak change in CSF fibrinogen was associated with the change in CSF interleukin (IL)-10 and IL-12p70. The peak change in CSF fibrinogen was associated with the change in CSF total tau (β=0.47, 95% CI 0.24-0.71, =0.002); however, we did not observe an association with postoperative delirium severity (incidence rate ratio = 1.20, 95% CI 0.66-2.17, =0.540).
Our preliminary findings support the hypothesis that fibrinogen enters the brain via blood-brain barrier disruption, promoting neuroinflammation and neuronal injury. However, we did not observe an association between cerebrospinal fluid fibrinogen and peak delirium severity in this limited cohort.
我们旨在评估脑脊液(CSF)中纤维蛋白原的围手术期变化、其与血脑屏障破坏和神经炎症标志物的关联以及与术后谵妄严重程度的关联。
我们对术后谵妄生物标志物2(IPOD - B2,NCT02926417)研究进行了二次分析,这是一项前瞻性观察队列研究。我们纳入了24例年龄大于21岁接受主动脉瘤修复术的患者。在手术前(n = 24)和手术后(n = 13)采集脑脊液样本,一些参与者有多个术后样本。我们的主要结局是脑脊液纤维蛋白原的围手术期变化。使用谵妄评定量表修订版98评估谵妄。
手术后脑脊液纤维蛋白原增加(P < 0.001),这与脑脊液/血浆白蛋白比值增加相关(β = 1.09,95%CI 0.47 - 1.71,P = 0.004)。脑脊液纤维蛋白原的峰值变化与脑脊液白细胞介素(IL)-10和IL - 12p70的变化相关。脑脊液纤维蛋白原的峰值变化与脑脊液总tau的变化相关(β = 0.47,95%CI 0.24 - 0.71,P = 0.002);然而,我们未观察到其与术后谵妄严重程度的关联(发病率比 = 1.20,95%CI 0.66 - 2.17,P = 0.540)。
我们的初步研究结果支持这样的假设,即纤维蛋白原通过血脑屏障破坏进入大脑,促进神经炎症和神经元损伤。然而,在这个有限的队列中,我们未观察到脑脊液纤维蛋白原与谵妄峰值严重程度之间的关联。