血清降钙素原对脓毒症早期诊断价值及预后意义的临床研究
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摘要
目的：探讨血清降钙素原(procalcitonin,PCT)对脓毒症早期诊断价值及预后意义。
1.于2008年12月-2009年4月收集天津医科大学总医院急诊医疗中心病例90例,根据脓毒症诊断标准分为脓毒症组(SEPSIS组)、非感染性全身炎症反应综合征组(SIRS组)和对照组,根据28天病死率将脓毒症组分为生存组和死亡组两个亚组。于入院后第1日、第3日晨时取血,动态观察PCT、C-反应蛋白(C-reactive protein,CRP)、红细胞沉降率(ESR)、白细胞(WBC)、中性粒细胞百分率(N)、血小板(PLT)、体温(T)等炎症指标变化；在脓毒症组中第1日、3日留取血清集中测定白介素-6(IL-6)、白介素-10(IL-10)水平变化。记录当日APACHEⅡ评分及SOFA评分。
2.PCT采用酶联荧光法(ELFA)测定,IL-6、IL-10采用双抗体免疫夹心法(ELISA)测定,CRP采用免疫比浊法测定。
3.统计学方法：数据以均数±标准差(x±s)或中位数及四分位数间距M(IQ)表示。计量资料数据先行1-K-S正态性检验,三组间数据符合正态分布采用单因素方差分析One-way ANOVA,两两比较采用LSD法,偏态分布采用Kruskal-Wallis H检验,两组间数据正态采用t检验,偏态采用Mann-Whitney U检验,计数资料采用χ2检验。相关性分析采用Spearman相关。绘制受试者特征操作曲线(receiver operator characteristic, ROC),比较曲线下面积大小,得出各个指标的最佳截断点及相应的灵敏度、特异度、阳性预测值和阴性预测值。在单因素比较后,对有差异的指标进行二分类多因素的Logistic回归分析,筛选出预后的独立危险因素。所有数据均由SPSS16.0、Medcalcll.3统计软件完成。P<0.05为差异有统计学意义。
1.脓毒症组患者第1日血清PCT水平高于SIRS组及对照组(p<0.05)；PCT的ROC曲线下面积(AUC)高于CRP、WBC、N、PLT、ESR、T。
2.在病原学方面,G-菌和G+菌及细菌和真菌的PCT水平无统计学差异。
3.死亡组患者第1日及第3日血清PCT水平均高于存活组(p=0.008,p=0.000)。
4.生存组PCT呈下降趋势直至正常,死亡组无明显下降趋势。
5.脓毒症组患者血清第1日PCT与APACHEⅡ、SOFA评分正性相关(r=0.487,p=0.000；r=0.508,p=0.000)。
6.ROC曲线分析,第1、3日的SOFA、APACHEⅡ、PCT的曲线下面积分别为：0.934、0.891、0.767及0.967、0.729、0.550,高于CRP、IL-6、IL-10、WBC、N、PLT、ESR、T。
7.Logistic回归分析,SOFA评分是死亡的独立危险因素。
1.血清PCT是脓毒症早期诊断的一个较好指标,其敏感性和特异性高于CRP、WBC、N、PLT、ESR、T等炎症指标,有助于鉴别非感染性全身炎症反应综合征和脓毒症。
2.血清PCT水平无助于G-菌和G+菌及细菌和真菌的分型。
3.血清PCT水平与脓毒症病情危重程度正性相关,其水平越高,病情越重。
4.动态监测血清PCT水平变化有助于判断脓毒症患者预后,其水平越高,预后越差,与SOFA、APACHEⅡ等危重系统评分联用具有更高的预测价值。
Objective:To investigate the early diagnostic value and prognostic significance of serum procalcitonin in patients with sepsis.
1.Collected 90 cases from emergency medical center of Tianjin Medical University General hospital between 2008 December and 2009 Aprial.According to the sepsis diagnosis criteria, the cases were divided into sepsis group、non-infectious systemic inflammatory response syndrome(sirs) group and control group. Meanwhile, the sepsis group were divided into two subgroups(survival group and death group) according to 28-day mortality. Monitored the dynamic changes of procalcitonin、C-reactive protein、IL-6、IL-10、erythrocyte sedimentation rate (ESR)、white blood cell(WBC)、neutrophil percentage(N)、platelet(PLT)、body temperature(T) on the 1st and 3rd day after admission.Recorded the acute physiology and chronic health evaluation(APACHEⅡ) and sequential organ failure assessment (SOFA).
2.PCT was measured by enzyme-linked fluorescent assay(ELFA),IL-6、IL-10 were measured by double-antibody sandwich ELISA,CRP level was measured by immunoturbidimetry.
3.Statistical analysis:The test data were expressed as frequencies for nominal variables and as mean±SD or medians with interquartile range for continuous variables.The data were performed 1-K-S normal distribution test.One-way ANOVA was used for three groups when the data were normal,and LSD method was used between two groups comparison. Kruskal- Wallis H test was used for nonparametric distribution data. The univariate analysis was performed using t test for means, Mann- Whitney U test for medians and chi-square test for categorical variables. Spearman p (rs) was calculated to assess the correlation between biomarkers and APACHEⅡ、SOFA score. The diagnostic accuracy of the PCT was evaluated by ROC curves.Those variables with p values less than 0.05 on univariate anlysis were then entered into a multivariate logistic regression analysis to further identify the independent predictors of 28-day mortality and their adjusted odds ratios (OR) with 95% confidence intervals(95%CI). SPSS16.0、Medcalc11.3 softwares were used for statistical analysis, and a two-tailed P-value< 0.05 was considered significant.
1.The serum procalcitonin of sepsis group on the 1 st day was higher than sirs and control groups; the area under ROC curve (AUC) of PCT was bigger than CRP、WBC、N、PLT、ESR and T.
2.There was no differcnce of PCT level between Gram-negative bacterium and Gram-positive bacterium and bacterium and fungus.
3.The PCT level of death group was higher than survival group on the 1st and 3rd day. (p=0.008, p=0.000,respectively)
4.The PCT level of survival group gradually declined to normal level,but the death group did not significantly decrease.
5.The PCT level of sepsis group on the 1st day positively correlated with APACHEⅡand SOFA. (r=0.487,p=0.000;r=0.508,p=0.00O,respectively).
6.The AUC of SOFA、APACHEⅡ、PCT on the 1st and 3rd day were 0.934、0.891、0.767 and 0.967、0.729、0.550.
7.The Logistic analysis showed SOFA was the independent predictor of 28-day mortality.
1.The accuracy of serum PCT was superior to other inflammatory biomarkers in the early diagnosis of sepsis,and it was helpful to differentiate noninfectious systemic inflammatory response syndrome and sepsis.
2.The serum PCT level could not help differentiate Gram-negative bacterium and Gram-positive bacterium and bacterium and fungus.
3.The serum PCT level can reflect severity of sepsis,the higher the PCT level was,the severer the patient's condition was.
4.Monitoring the dynamic changes of serum PCT level was useful to judge prognosis of sepsis patients, the higher the PCT level was,the worse the outcome was.And it could provide more clinical information when used with SOFA APACHEⅡscores together.
1.于2008年12月-2009年4月收集天津医科大学总医院急诊医疗中心病例90例,根据脓毒症诊断标准分为脓毒症组(SEPSIS组)、非感染性全身炎症反应综合征组(SIRS组)和对照组,根据28天病死率将脓毒症组分为生存组和死亡组两个亚组。于入院后第1日、第3日晨时取血,动态观察PCT、C-反应蛋白(C-reactive protein,CRP)、红细胞沉降率(ESR)、白细胞(WBC)、中性粒细胞百分率(N)、血小板(PLT)、体温(T)等炎症指标变化；在脓毒症组中第1日、3日留取血清集中测定白介素-6(IL-6)、白介素-10(IL-10)水平变化。记录当日APACHEⅡ评分及SOFA评分。
2.PCT采用酶联荧光法(ELFA)测定,IL-6、IL-10采用双抗体免疫夹心法(ELISA)测定,CRP采用免疫比浊法测定。
3.统计学方法：数据以均数±标准差(x±s)或中位数及四分位数间距M(IQ)表示。计量资料数据先行1-K-S正态性检验,三组间数据符合正态分布采用单因素方差分析One-way ANOVA,两两比较采用LSD法,偏态分布采用Kruskal-Wallis H检验,两组间数据正态采用t检验,偏态采用Mann-Whitney U检验,计数资料采用χ2检验。相关性分析采用Spearman相关。绘制受试者特征操作曲线(receiver operator characteristic, ROC),比较曲线下面积大小,得出各个指标的最佳截断点及相应的灵敏度、特异度、阳性预测值和阴性预测值。在单因素比较后,对有差异的指标进行二分类多因素的Logistic回归分析,筛选出预后的独立危险因素。所有数据均由SPSS16.0、Medcalcll.3统计软件完成。P<0.05为差异有统计学意义。
1.脓毒症组患者第1日血清PCT水平高于SIRS组及对照组(p<0.05)；PCT的ROC曲线下面积(AUC)高于CRP、WBC、N、PLT、ESR、T。
2.在病原学方面,G-菌和G+菌及细菌和真菌的PCT水平无统计学差异。
3.死亡组患者第1日及第3日血清PCT水平均高于存活组(p=0.008,p=0.000)。
4.生存组PCT呈下降趋势直至正常,死亡组无明显下降趋势。
5.脓毒症组患者血清第1日PCT与APACHEⅡ、SOFA评分正性相关(r=0.487,p=0.000；r=0.508,p=0.000)。
6.ROC曲线分析,第1、3日的SOFA、APACHEⅡ、PCT的曲线下面积分别为：0.934、0.891、0.767及0.967、0.729、0.550,高于CRP、IL-6、IL-10、WBC、N、PLT、ESR、T。
7.Logistic回归分析,SOFA评分是死亡的独立危险因素。
1.血清PCT是脓毒症早期诊断的一个较好指标,其敏感性和特异性高于CRP、WBC、N、PLT、ESR、T等炎症指标,有助于鉴别非感染性全身炎症反应综合征和脓毒症。
2.血清PCT水平无助于G-菌和G+菌及细菌和真菌的分型。
3.血清PCT水平与脓毒症病情危重程度正性相关,其水平越高,病情越重。
4.动态监测血清PCT水平变化有助于判断脓毒症患者预后,其水平越高,预后越差,与SOFA、APACHEⅡ等危重系统评分联用具有更高的预测价值。
Objective:To investigate the early diagnostic value and prognostic significance of serum procalcitonin in patients with sepsis.
1.Collected 90 cases from emergency medical center of Tianjin Medical University General hospital between 2008 December and 2009 Aprial.According to the sepsis diagnosis criteria, the cases were divided into sepsis group、non-infectious systemic inflammatory response syndrome(sirs) group and control group. Meanwhile, the sepsis group were divided into two subgroups(survival group and death group) according to 28-day mortality. Monitored the dynamic changes of procalcitonin、C-reactive protein、IL-6、IL-10、erythrocyte sedimentation rate (ESR)、white blood cell(WBC)、neutrophil percentage(N)、platelet(PLT)、body temperature(T) on the 1st and 3rd day after admission.Recorded the acute physiology and chronic health evaluation(APACHEⅡ) and sequential organ failure assessment (SOFA).
2.PCT was measured by enzyme-linked fluorescent assay(ELFA),IL-6、IL-10 were measured by double-antibody sandwich ELISA,CRP level was measured by immunoturbidimetry.
3.Statistical analysis:The test data were expressed as frequencies for nominal variables and as mean±SD or medians with interquartile range for continuous variables.The data were performed 1-K-S normal distribution test.One-way ANOVA was used for three groups when the data were normal,and LSD method was used between two groups comparison. Kruskal- Wallis H test was used for nonparametric distribution data. The univariate analysis was performed using t test for means, Mann- Whitney U test for medians and chi-square test for categorical variables. Spearman p (rs) was calculated to assess the correlation between biomarkers and APACHEⅡ、SOFA score. The diagnostic accuracy of the PCT was evaluated by ROC curves.Those variables with p values less than 0.05 on univariate anlysis were then entered into a multivariate logistic regression analysis to further identify the independent predictors of 28-day mortality and their adjusted odds ratios (OR) with 95% confidence intervals(95%CI). SPSS16.0、Medcalc11.3 softwares were used for statistical analysis, and a two-tailed P-value< 0.05 was considered significant.
1.The serum procalcitonin of sepsis group on the 1 st day was higher than sirs and control groups; the area under ROC curve (AUC) of PCT was bigger than CRP、WBC、N、PLT、ESR and T.
2.There was no differcnce of PCT level between Gram-negative bacterium and Gram-positive bacterium and bacterium and fungus.
3.The PCT level of death group was higher than survival group on the 1st and 3rd day. (p=0.008, p=0.000,respectively)
4.The PCT level of survival group gradually declined to normal level,but the death group did not significantly decrease.
5.The PCT level of sepsis group on the 1st day positively correlated with APACHEⅡand SOFA. (r=0.487,p=0.000;r=0.508,p=0.00O,respectively).
6.The AUC of SOFA、APACHEⅡ、PCT on the 1st and 3rd day were 0.934、0.891、0.767 and 0.967、0.729、0.550.
7.The Logistic analysis showed SOFA was the independent predictor of 28-day mortality.
1.The accuracy of serum PCT was superior to other inflammatory biomarkers in the early diagnosis of sepsis,and it was helpful to differentiate noninfectious systemic inflammatory response syndrome and sepsis.
2.The serum PCT level could not help differentiate Gram-negative bacterium and Gram-positive bacterium and bacterium and fungus.
3.The serum PCT level can reflect severity of sepsis,the higher the PCT level was,the severer the patient's condition was.
4.Monitoring the dynamic changes of serum PCT level was useful to judge prognosis of sepsis patients, the higher the PCT level was,the worse the outcome was.And it could provide more clinical information when used with SOFA APACHEⅡscores together.
引文
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[10]. Nylen ES,Whang KT,Snider RH Jr, et al. Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis[J].Crit Care Med,1998,26:1001-1006.
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