Sepsis-3精确性和实用性的多中心验证

A multicenter confirmatory study about precision and practicability of Sepsis-3

目的对脓毒症3.0（Sepsis-3）诊断标准的精确性进行临床验证，以指导和推广其临床应用。方法采用多中心回顾性研究方法，选择2015年1月至6月浙江省6家三甲医院重症加强治疗病房（ICU）收治的患者，筛选出符合Sepsis-2和Sepsis-3诊断标准者，比较符合两个版本指南患者的人群特征，并观察不同医院诊断率的差异。根据医生诊断情况，将符合Sepsis-2诊断标准的患者分为诊断组和非诊断组，采用logistic回归分析影响医生诊断脓毒症的相关因素。将符合Sepsis-2但不符合Sepsis-3的患者作为排除组，同时符合Sepsis-3的患者作为入选组，比较两组患者的基本特征。绘制受试者工作特征曲线（ROC），分析全身炎症反应综合征（SIRS）评分、快速序贯器官衰竭评分（qSOFA）、序贯器官衰竭评分（SOFA）对患者死亡的预测价值，并对比分析qSOFA与SOFA的一致性是否会影响诊断的敏感度。将Sepsis-2患者分为死亡组和存活组，采用logistic回归分析与死亡相关的因素。结果最终入选1？423例患者，其中3例年龄〈18岁、19例数据缺失，均排除；符合Sepsis-2和Sepsis-3诊断标准者分别为363例和329例，两组患者人群特征比较，除急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分有显著差异〔分：19.10（8.00）比20.28（8.00），P〈0.05〕外，其余指标差异均无统计学意义。对各医院分析显示，医院3中Sepsis-2和Sepsis-3患者28 d病死率最高（分别为60.4%、60.0%），诊断率最低（为0）；而医院1患者28 d病死率最低（分别为22.9%、27.2%），但诊断率只有19.5%；医院4诊断率高达44.8%，但28 d病死率却均达58.6%。logistic回归分析显示，年龄大〔优势比（OR）＝0.970，P＝0.021〕、血乳酸高（OR＝0.443，P＝0.004）、血压高（OR＝0.957，P＝0.009）、氧合指数低（OR＝1.004，P＝0.024）的患者更容易被忽视诊断。与Sepsis-3排除组比较，Sepsis-3入选组患者年龄更大〔岁：68.52（26.00）比53.75（18.00），P〈0.01〕，APACHEⅡ评分更高〔分：20.28（8.00）比7.72（6.00），P〈0.01〕，血乳酸更高〔mmol/L：3.45（3.00）比1.95（1.20），但P〉0.05〕，ICU住院时间更长〔d：22.42（22.00）比15.13（16.00），P〈0.01〕，28 d病死率更高〔45.29%（149/329）比14.71%（5/34），P〈0.01〕，说明Sepsis-2的诊断效能较低，而Sepsis-3诊断特异度更高，且Sepsis-3患者预后更差。ROC曲线分析显示，SIRS、qSOFA、SOFA评分对死亡的预测价值依次升高〔ROC曲线下面积（AUC）分别为0.567、0.597、0.683〕，但预测价值均较低。将Sepsis-2中符合qSOFA、SOFA其中一项组与符合两项组患者进行比较，结果显示，两组APACHEⅡ评分〔分：17.55（7.00）比23.24（8.00）〕和28 d病死率〔38.75%（31/80）比58.59%（75/128）〕存在统计学差异（均P〈0.01），仅满足一项的患者28 d病死率也高达38.75%，提示在临床工作中，即使只有qSOFA出现异常也应引起足够的重视。与存活组比较，死亡组患者年龄更大，APACHEⅡ评分更高，ICU住院时间更短（均P〈0.05）；logistic回归分析显示，与死亡相关的因素有APACHEⅡ评分（OR＝1.199，P＝0.000）和ICU住院时间（OR＝0.949，P＝0.000）。结论Sepsis-3筛选出的患者倾向于器官功能障碍，对死亡的预测价值较Sepsis-2更高，且诊断特异度提高，但数据显示仍然有改进空间。

ObjectiveTo clinically validate the precision of diagnostic Sepsis-3 criteria, and to guide and generalize its clinical application.MethodsA multicenter retrospective observational study was conducted. The patients admitted to intensive care unit （ICU） of 6 tertiary hospitals in Zhejiang Province from January to June 2015 were enrolled, and the patients satisfying the diagnostic criteria of Sepsis-2 and Sepsis-3 were screened. Population characteristics between the patients satisfying two editions were compared, and the diagnosis accuracy rate in different degree hospitals were investigated. According to the doctor＇s diagnosis, the patients who met the criteria of Sepsis-2 were divided into diagnosis group and non-diagnosis group, and the factors influencing the diagnosis of sepsis were analyzed by logistic regression. The patients meeting Sepsis-2 but no meeting Sepsis-3 were served as exclusion group, and those meeting Sepsis-2 and Sepsis-3 were served as enroll group, and the characteristics of patients between the two groups were compared. Receiver operating characteristic （ROC） curve was plotted to evaluate the predictive value of systemic inflammatory response syndrome （SIRS） score, sepsis-related quick sequential organ failure assessment （qSOFA） and sequential organ failure assessment （SOFA） on death, and whether the consistency of qSOFA and SOFA would affect the sensitivity of definition. The patients meeting Sepsis-2 were divided into non-survived group and survived group, and the factors associated with death were analyzed by logistic regression.ResultsFinally, 1？423 patients were enrolled, 3 patients with age 〈 18 years and 19 patients with missing data were excluded. There were 363 patients and 329 patients met Sepsis-2 and Sepsis-3, respectively. No significant differences were found in population characteristics between the groups of Sepsis-2 and Sepsis-3 （all P 〉 0.05） except for acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score [19.10 （8.00） vs. 20.28 （8.00）, P 〈 0.05]. It was shown on the clinical data analysis of the hospitals that the patients meeting Sepsis-2 and Sepsis-3 in hospital 3 had the highest 28-day mortality （60.4% and 60.0%） with the lowest rate of diagnosis （0）. While in the hospital 1, the patients had the lowest 28-day mortality （22.9% and 27.2%）, and the rate of diagnosis was 19.5%. Interestingly, the patients in hospital 4 had the highest diagnosis rate of sepsis （44.8%）, but 28-day mortality was both 58.6%. It was shown by logistic regression analysis that the patients with old age [odds ratio （OR） = 0.970, P = 0.021], high blood lactate （OR = 0.443, P = 0.004）, high blood pressure （OR = 0.957, P = 0.009） and low oxygenation index （OR = 1.004, P = 0.024） were easy to neglect diagnosis. Compared with Sepsis-3 exclude group, the patients in Sepsis-3 enroll group were older [years： 68.52 （26.00） vs. 53.75 （18.00）, P 〈 0.01] with higher APACHEⅡ score [20.38 （8.00） vs. 7.72 （6.00）, P 〈 0.01], higher blood lactate [mmol/L： 3.45 （3.00） vs. 1.95 （1.20）, P 〉 0.05], longer length of ICU stay [days： 22.42 （22.00） vs. 15.13 （16.00）, P 〈 0.01], and higher 28-day mortality [45.29% （149/329） vs. 14.71% （5/34）, P 〈 0.01], indicating that the diagnostic efficiency of Sepsis-2 was low, the diagnostic specificity of Sepsis-3 was high, and the prognosis of Sepsis-3 patients was worse. It was shown by ROC curve analysis that the prognostic value of SIRS, qSOFA and SOFA to mortality was gradually increased [area under ROC curve （AUC） was 0.567, 0.597, 0.683, respectively], but the prognostic value were all low. Comparing patients meeting qSOFA and （or） SOFA in Sepsis-2, significant differences were found in APACHE Ⅱ score [17.55 （7.00） vs. 23.24 （8.00）] and 28-day mortality [38.75% （31/80） vs. 58.59% （75/128）, both P 〈 0.01]. The patients who just met the qSOFA or SOFA, their 28-day mortality was up to 38.75%, suggesting that qSOFA should not be ignored. Compared with survived group, the patients in survived group were older with higher APACHE Ⅱ score and shorter length of ICU stay （all P 〈 0.05）. It was shown by logistic regression analysis that APACHE Ⅱ score （OR = 1.199, P = 0.000） and length of ICU stay （OR = 0.949, P = 0.000） were related with death.ConclusionPatients satisfied Sepsis-3 were easier to develop more organ failure, Sepsis-3 and higher death prediction than Sepsis-2 and higher diagnosis specificity, but data shows that there is extra room for improvement.