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  新医学  2016, Vol. 47 Issue (10): 681-685  DOI: 10.3969/j.issn.0253-9802.2016.10.007
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梅华鲜 , 李永胜 , 陈正平 , 黄中会 , 刘凤丹 . 2016. 毛细血管渗漏指数在脓毒症并ARDS早期诊断中的应用[J]. 新医学, 47(10): 681-685. DOI: 10.3969/j.issn.0253-9802.2016.10.007.
[复制中文]
Mei Huaxian , Li Yongsheng , Chen Zhengping , Huang Zhonghui , Liu Fengdan . 2016. Application of CLI in the early diagnosis of sepsis complicated with ARDS[J]. Journal of New Medicine, 47(10): 681-685. DOI: 10.3969/j.issn.0253-9802.2016.10.007.
[复制英文]

通讯作者

李永胜，E-mail:ysli@tjh.tjmu.edu.cn

文章历史

收稿日期：2016-06-06
Contents              Abstract              Full text              Figures/Tables              PDF
毛细血管渗漏指数在脓毒症并ARDS早期诊断中的应用
梅华鲜 , 李永胜 , 陈正平 , 黄中会 , 刘凤丹     
430030 武汉，华中科技大学同济医学院附属同济医院急诊/重症医学科
收稿日期：2016-06-06
通讯作者：李永胜，E-mail:ysli@tjh.tjmu.edu.cn
摘要: 目的 探讨毛细血管渗漏指数(CLI)对于预测脓毒症患者并发ARDS的临床价值。 方法 回顾性分析ICU收治的脓毒症患者288例，检测患者入院时的CRP、血清白蛋白，并记录其余各项生理及实验室指标，根据是否并发ARDS分为ARDS组和非ARDS组，比较2组患者肺损伤预测评分(LIPS)、CLI有无差异，并行Logistic回归分析确定预测脓毒症患者并发ARDS的独立危险因素，采用受试者工作特征(ROC)曲线下面积(AUC)法比较各指标对ARDS早期诊断的价值。 结果 ARDS组患者血乳酸、CRP、CLI、LIPS、APACHEⅡ评分及病死率均高于非ARDS组，白蛋白低于非ARDS组，差异具有统计学意义(P均 < 0.05)。多因素回归分析显示CLI、LIPS是预测脓毒症患者并发ARDS的独立危险因素。ROC曲线法分析显示CLI、LIPS预测ARDS的价值较大。CLI的AUC为0.807(95%CI 0.757～0.856)，最佳截断点4.99，此时敏感度为86.3%，特异度为63.4%；LIPS的AUC为0.823(95%CI 0.775～0.870)，最佳截断值为5.25，此时敏感度91.1%，特异度58.5%。 结论 CLI更简单易得，可以作为预测脓毒症患者并发ARDS的较好指标。
关键词: 脓毒症    急性呼吸窘迫综合症    毛细血管渗漏指数    预测指标    
Application of CLI in the early diagnosis of sepsis complicated with ARDS
Mei Huaxian , Li Yongsheng , Chen Zhengping , Huang Zhonghui , Liu Fengdan     
Tongji Hospital Affiliated to Tongji Medical University, Huazhong University of Science and Technology, Wuhan 430030, China
Corresponding author: Li Yongsheng, E-mail:ysli@tjh.tjmu.edu.cn
Abstract: Objective To explore the clinical value of capillary leakage index (CLI) in the prediction of sepsis complicated with acute respiratory distress syndrome (ARDS). Methods Clinical data of 288 sepsis patients admitted in the intensive care unit (ICU) of our hospital were retrospectively analyzed. Serum C-reactive protein (CRP), albumin and other psychological and laboratory indexes were collected upon admission. All patients were divided into the ARDS and non-ARDS groups. The lung injury prediction score (LIPS) and CLI were statistically compared between two groups. Logistic regression analysis was used to determine the independent risk factors for sepsis complicated with ARDS. Clinical values of each index in the early diagnosis of ARDS were evaluated with the areas under the receiver operating characteristics (ROC) curve (AUC). Results Compared with the non-ARDS group, the lactate level, CRP level, CLI, LIPS, APACHEII score and mortality were significantly higher whereas the albumin level was considerably lower in the ARDS group (all P < 0.05). Multi-variate logistic regression revealed that CLI and LIPS were the independent risk factors of sepsis complicated with ARDS. ROC curve analysis demonstrated that the values of CLI and LIPS in predicting ARDS occurrence were relatively significant. The AUC of CLI was 0.807 (95% CI 0.757-0.856). The optimal cut-off value was 4.99 with sensitivity of 86.3% and specificity of 63.4%. The AUC of LIPS was 0.823 (95% CI 0.775-0.870). The optimal cut-off value was 5.25 with sensitivity of 91.1% and specificity of 58.5%. Conclusions CLI is a simple and convenient index, which can be utilized to predict the incidence of sepsis complicated with ARDS.
Key words: Sepsis    Acute respiratory distress syndrome    Capillary leakage index    Predictor[1] Williams JP, Mcbride WH. After the bomb drops: a new look at radiation-induced multiple organ dysfunction syndrome (MODS). Int J Radiat Biol, 2011, 87(8): 851-868.    

ARDS是临床常见的急危重症，其发病急，病情进展快，治疗棘手，死亡率高[1-2]。脓毒症是机体感染微生物后引起的失控性全身炎症反应，是急性肺损伤(ALI)/ARDS的重要易感因素；肺脏是脓毒症中最易受累的靶器官[3]。虽然ARDS的诊疗技术不断进步，但其病死率并没有明显下降；因此对ARDS的提前预测及早期干预尤显重要[4]。研究表明毛细血管渗漏指数(CLI)可以评估脓毒症患者毛细血管的通透性大小，而ARDS的病理特征之一即为肺微血管通透性增高，CLI是否能够成为预测脓毒症患者并发ARDS的指标，值得进一步研究[5-7]。

对象与方法 一、研究对象

选取2014年1月至2016年4月我院ICU收治的脓毒症患者288例，其中男168例、女120例，年龄18～98岁、中位年龄59岁。脓毒症的诊断参照2012年《国际严重脓毒症和脓毒症休克指南》[8]。排除年龄 < 18岁，住院时间 < 48 h的病例。ARDS的诊断采用2011年柏林新标准[9]。CLI定义为CRP(mg/dl)与血清白蛋白(g/L)的比值×100[5]。肺损伤预测评分(LIPS)的赋值标准见表 1。

表 1 LIPS赋值标准
二、研究方法

对符合入选脓毒症纳入标准的患者，入院后均记录其一般资料(性别、年龄、吸烟、饮酒史、基础疾病)、生命体征指标、并常规送检血常规、血生化、留取病原学标本并行相关培养。取入院24 h最差值行急性生理功能和慢性健康状况评分系统Ⅱ(APACHEⅡ)，入院当天行LIPS评分。根据是否合并ARDS分2组，ARDS组和非ARDS组。追踪每例患者28 d的生存结局。

三、统计学处理

应用SPSS 19.0统计软件进行分析，正态分布的计量资料以x±s表示，组间比较采用t检验；非正态分布的计量资料以中位数(四分位数间距)表示，采用非参数检验；计数资料采用χ2检验。利用Logistic回归分析确定预测脓毒症死亡的独立因素；绘制受试者工作特征(ROC)曲线，比较各指标ROC曲线下面积(AUC)。P < 0.05为差异有统计学意义。

结果 一、2组患者的临床资料比较

2组患者的年龄、性别、基础疾病、感染的部位相比，差异均无统计学意义(P均>0.05)，具有可比性。ARDS患者的乳酸、CRP、CLI、LIPS、APACHEⅡ评分及病死率均高于非ARDS组，血清白蛋白水平低于非ARDS组，差异均具有统计学意义(P均 < 0.05)，见表 2。

表 2 ARDS组与非ARDS组患者的临床资料比较
二、脓毒症并发ARDS的多因素回归分析

选取2组间有统计学差异的乳酸、ALB、CRP、CLI、LIPS分别作为协变量，以脓毒症并发ARDS作为因变量行Logistic回归分析，结果显示CLI、LIPS是预测脓毒症患者并发ARDS的独立危险因素，见表 3。

表 3 预测脓毒症患者发生ARDS的Logistic回归分析
三、CLI、LIPS预测脓毒症并发ARDS的ROC曲线

将Logistic回归分析所得的各指标对各个体预测概率作为ROC曲线协变量，以是否合并ARDS作为因变量，得到CLI的AUC为0.807(95%CI 0.757～0.856)，最佳截断点4.99，此时敏感度为86.3%，特异度为63.4%；LIPS的AUC为0.823(95%CI 0.775～0.870)，最佳截断值为5.25，此时敏感度91.1%，特异度58.5%。见图 1。

图 1 CLI、LIPS预测脓毒症并发ARDS的ROC曲线
讨论

本研究回顾性分析我院ICU收入的288例脓毒症患者的临床资料，其中合并ARDS的患者124例，发病率为43.05%，略高于国外文献报道的40%，考虑与纳入的对象有关，危重患者发生ARDS的机率可能更高[10]。与非ARDS组相比，ARDS组患者的APACHEⅡ评分、死亡率更高。一项来自中国22个大型综合医院ICU的流行病学调查显示，严重脓毒症或脓毒性休克所致的ALI/ARDS是导致患者死亡的独立危险因素，因而临床医师需提高对此类患者的重视[11]。

尽管目前ARDS的治疗策略在不断改进和更新，其病死率仍高达40%，究其根源是该疾病的发病机制尚未完全阐明，缺乏可以早期诊断的特异敏感指标及疗效确切的治疗措施[12-13]。如何提高ARDS的抢救成功率一直是临床研究的热点和难点。鉴于ARDS的治疗手段有限，目前越来越多的学者认识到，早期诊断早期预防可能对ARDS的治疗有着更为重要的意义[14]。

本研究对脓毒症患者合并ARDS的危险因素行多因素回归分析结果显示，LIPS、CLI是脓毒症患者并发ARDS的独立预测因子。ROC曲线分析结果也显示两者具有较好的预测效能(AUC分别为0.823、0.807)。

LIPS评分是Gajic等[15]于2011年提出的用于预测患者发生ALI的模型。该系统从易感因素、高风险手术、创伤和风险修正等方面进行评分，认为评分越高越容易发生ARDS。该模型数据在患者入院早期即可获得，与是否机械通气无关，具有较好的操作性、可实践性。经临床检验，其具有较好的预测ALI的效力(文献报道其AUC在0.79～0.84)，与本研究结果大致相仿[16-17]。

CLI是临床上用于评估毛细血管通透性大小的指标。脓毒症时，大量炎症因子和炎症介质的释放和活化，导致全身多系统、失控性的毛细血管渗漏，血浆白蛋白等胶体物质也可从血管内渗出到组织间隙，一方面导致严重低蛋白血症，血管内胶体渗透压下降，另一方面组织间隙胶体渗透压增加，更多的水分外渗，也加重了间质水肿程度[18]。肺通常是最早受累的器官，且发生率最高，临床表现为ALI或ARDS[19]。因此，就其本质来说，ARDS是机体炎症反应失控的结果，是SIRS的肺部表现。CLI由2部分组成，CRP是机体炎症反应的敏感指标，而血浆白蛋白是维持血管内胶体渗透压的主要成分，同时具有抗炎、抗氧化、抗休克、协调维持血管内皮完整性的作用[20-21]。CLI结合了两者的优势，同时反映全身的炎症程度及血清白蛋白的水平，故可能成为预测ARDS的较好指标。

综上所述，CLI是预测脓毒症并发ARDS的较好指标。相比于LIPS众多的评判项目来说，CLI更简单易得，有着更好的操作性，值得临床推广应用。尤其对于急诊、重症医学医生来说，更有利于对病情作出快速准确的判断，从而大大提高抢救的效率。

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