Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.
Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.
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DOI：
10.1016/j.biopsych.2016.03.2098
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发表时间：
2017-01-15
影响因子：
10.6
通讯作者：
Libermann TA
中科院分区：
文献类型：
--
作者：
Dillon ST;Vasunilashorn SM;Ngo L;Otu HH;Inouye SK;Jones RN;Alsop DC;Kuchel GA;Metzger ED;Arnold SE;Marcantonio ER;Libermann TA
谵妄是一种常见的，病态的，昂贵的术后并发症。我们的目的是确定血液为基础的术后谵妄标记物在巢式病例对照研究中的老年手术患者使用蛋白质组学方法，然后用酶联免疫吸附试验（ELISA）验证。择期手术后成功老化研究招募了年龄≥70岁、接受重大计划非心脏手术的无痴呆成年人（N=566; 24%谵妄）。在4个时间点采集血浆：术前（PREOP）、麻醉后监护室（PACU）、术后第2天（POD 2）和1个月随访（PO 1 MO）。为独立发现（39对）和复制队列（36对）选择匹配的对，随后将其合并为合并队列（75对）。进行基于iTRAQ的相对定量质谱蛋白质组学来鉴定最强的谵妄相关蛋白，并选择该蛋白进行ELISA验证。使用ELISA结果，在所有队列中使用非参数符号秩检验进行统计分析，检查鉴定的蛋白质与谵妄之间的关联。C-反应蛋白（CRP）从蛋白质组学分析中脱颖而出，成为最强的谵妄相关蛋白。ELISA验证证实，与对照组相比，病例组的CRP水平显著升高（*p<.05，**p<.01）在PREOP时的发现、复制和合并队列中（中位配对差异[mg/L]分别为1.97*、0.29、1.56**），PACU（分别为2.83、2.22*、2.53**）和POD 2（分别为71.97**、35.18*、63.76**），但不包括PO 1 MO（分别为2.72、-0.66、1.10）。术前和术后血浆CRP水平升高与谵妄相关，表明炎症前状态和对手术的炎症反应升高是谵妄的潜在病理生理机制。
Delirium is a common, morbid, and costly postoperative complication.. We aimed to identify blood-based postoperative delirium markers in a nested case control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. The Successful Aging after Elective Surgery Study enrolled dementia-free adults age ≥70 undergoing major scheduled non-cardiac surgery (N=566; 24% delirium). Plasma was collected at 4 timepoints: preoperatively (PREOP), post-anesthesia care unit (PACU), postoperative day 2 (POD2) and 1 month follow-up (PO1MO). Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). iTRAQ-based relative quantitation mass spectrometry proteomics was performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using non-parametric signed-rank tests were performed in all cohorts examining the association between the identified protein and delirium. C-reactive protein (CRP) emerged from the proteomics analysis as the strongest delirium-related protein. ELISA validation confirmed that compared to controls, cases had significantly higher CRP levels (*p<.05, **p<.01) in the discovery, replication, and pooled cohorts at PREOP (median paired difference [mg/L] 1.97*, 0.29, 1.56**, respectively), PACU (2.83, 2.22*, 2.53**, respectively) and POD2 (71.97**, 35.18*, 63.76**, respectively), but not PO1MO (2.72, −0.66, 1.10, respectively). Elevated pre- and postoperative plasma levels of CRP were associated with delirium, suggesting that a pre-inflammatory state and heightened inflammatory response to surgery are potential pathophysiological mechanisms of delirium.
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影响因子：
120.7
作者：
Marcantonio, Edward R.
通讯作者：
Marcantonio, Edward R.
影响因子：
7
作者：
Ritchie, C. W.;Newman, T. H.;Sampson, E. L.
通讯作者：
Sampson, E. L.
影响因子：
1.5
作者：
Pol, Robert A.;van Leeuwen, Barbara L.;Zeebregts, Clark J.
通讯作者：
Zeebregts, Clark J.
影响因子：
6.3
作者：
Saczynski JS;Kosar CM;Xu G;Puelle MR;Schmitt E;Jones RN;Marcantonio ER;Wong B;Isaza I;Inouye SK
通讯作者：
Inouye SK
影响因子：
3.5
作者：
Beloosesky, Y;Grinblat, J;Hendel, D
通讯作者：
Hendel, D