Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia.
Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Br J Anaesth. 2022 Aug;129(2):219-230. doi: 10.1016/j.bja.2022.01.005. Epub 2022 Feb 8.
Case-control studies have associated delirium with blood-brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity.
Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate.
The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P<0.001), delirium incidence (CPAR P=0.012; S100B P<0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P<0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01).
Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB.
病例对照研究表明，谵妄与血脑屏障（BBB）通透性有关。然而，这种方法无法确定谵妄是归因于预先存在的高通透性还是围手术期的变化。我们检测了脑脊液/血浆白蛋白比值（CPAR）和血浆 S100B 的围手术期变化是否与谵妄严重程度有关。
参与者被招募到两项非颅内手术的前瞻性队列研究中（NCT01980511、NCT03124303 和 NCT02926417）。使用 Delirium Rating Scale-98 评估谵妄严重程度。使用 3D 混淆评估方法（3D-CAM）或 ICU-CAM（ICU 用 CAM）诊断谵妄发生率。对 25 例患者的脑脊液样本和 78 例患者的血浆样本进行白蛋白和 S100B 分析。我们检测了 CPAR（n=11）和 S100B（n=61）的变化与谵妄、失血量、CSF 白细胞介素-6（IL-6）和 CSF 乳酸之间的关联。
CPAR 和 S100B 的围手术期增加与谵妄严重程度相关（CPAR ρ=0.78，P=0.01；S100B ρ=0.41，P<0.001），与谵妄发生率（CPAR P=0.012；S100B P<0.001）和 CSF IL-6（CPAR ρ=0.66，P=0.04；S100B ρ=0.75，P=0.025）相关。线性混合效应分析还表明，S100B 水平降低预测谵妄症状的恢复（P=0.001）。线性回归表明，血浆 S100B 的变化与手术风险、心血管手术、失血量和低血压独立相关。失血量也与 CPAR（ρ=0.64，P=0.04）、S100B（ρ=0.70，P<0.001）、CSF 乳酸（R=0.81，P=0.01）和谵妄严重程度峰值（ρ=0.36，P=0.01）相关。
术后谵妄与 BBB 破裂有关。这种通透性的增加是动态的，并与神经炎症和乳酸反应有关。减少失血量的策略可能有助于保护 BBB。
