心脏手术后的术中氧化损伤与谵妄。
Intraoperative Oxidative Damage and Delirium after Cardiac Surgery.
机构信息
From the Divisions of Anesthesiology Critical Care Medicine (M.G.L., C.G.H., F.T.B.) Cardiothoracic Anesthesiology (J.B.O., F.T.B.), Department of Anesthesiology Department of Biostatistics (M.S.S., J.M.) Department of Cardiac Surgery (M.R.P., A.S.S.) Divisions of Allergy, Pulmonary, and Critical Care Medicine (J.B.M.) Clinical Pharmacology (A.D., N.J.B., F.T.B.), Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
出版信息
Anesthesiology. 2020 Mar;132(3):551-561. doi: 10.1097/ALN.0000000000003016.
BACKGROUND
Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations.
METHODS
In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations.
RESULTS
Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049).
CONCLUSIONS
Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.
背景
术后谵妄的发生机制仍知之甚少，这限制了有效治疗方法的发展。我们检验了以下假说，即术中氧化损伤与谵妄和神经元损伤有关，而血脑屏障的破坏会改变这些关联。
方法
在一项针对 400 名接受心脏手术的患者的前瞻性队列研究中，这些患者被纳入阿托伐他汀降低肾损伤和谵妄的临床试验，我们使用气相色谱-质谱法测量血浆中二氢呋喃和 F2-异前列腺素的浓度，以量化氧化损伤；用酶联免疫吸附试验测量 S100 钙结合蛋白 B，以量化血脑屏障的破坏；用乌头羧酸基末端水解酶同工酶 L1 量化神经元损伤。我们在手术前后进行两次每日 ICU 意识混乱评估法来诊断谵妄。我们测量了术中 F2-异前列腺素和二氢呋喃与谵妄（主要结局）和术后乌头羧酸基末端水解酶同工酶 L1（次要结局）之间的独立关联，并评估了 S100 钙结合蛋白 B 是否改变了这些关联。
结果
在 400 名患者中，有 109 名（27.3%）患者发生谵妄，中位数（第 10 分位、第 90 分位）为 1.0（0.5，3.0）天。在总队列中，基线时乌头羧酸基末端水解酶同工酶 L1 的浓度为 6.3ng/ml（2.7，14.9），术后第 1 天为 12.4ng/ml（7.9，31.2）。二氢呋喃和 F2-异前列腺素在整个手术过程中均增加，术中 F2-异前列腺素和二氢呋喃的对数总和与术后谵妄的几率增加独立相关（比值比，3.70[95%CI，1.41 至 9.70]；P=0.008），与术后乌头羧酸基末端水解酶同工酶 L1 的比值也相关（几何均数比，1.42[1.11 至 1.81]；P=0.005）。在 S100 钙结合蛋白 B 升高的患者中，F2-异前列腺素和二氢呋喃增加与术后乌头羧酸基末端水解酶同工酶 L1 增加之间的关联更为显著（P=0.049）。
结论
术中氧化损伤与术后谵妄和神经元损伤有关，而在血脑屏障破坏增加的患者中，氧化损伤与神经元损伤之间的关联更强。
Zotero 插件