| Research backgroundSepsis is the systemic inflammatory response to infection syndrome caused by microbial invasion of the body,the incidence is burn,infection,surgical operation complications,intensive care unit(ICU)is the most common in critically ill patients,can rapidly progress to syndrome and septic shock,multiple organ failure in serious condition,high death rate.Motherland medicine thinks,sepsis is due to the internal(deficiency)and external(Xiedu invasion)the result of joint action,pathogenesis is deficiency of toxins,toxic heat,blood stasis,phlegm stasis context,qi movement disturbance,viscera function disorder.Wang Jinda in the "three cards three law" as the research breakthrough point,namely,heat toxin syndrome with heat clearing and detoxicating,in application of activating blood to remove stasis,acute deficiency syndrome with Fuzheng equity method treatment,and achieved remarkable curative effect.Xuebijing injection is an important representative of promoting blood circulation to remove blood stasis,with Xuefu Zhuyu decoction as the foundation,the main components of Radix Paeoniae Rubra,Rhizoma Chuanxiong,radix salviae miltiorrhizae,safflower,angelica Huoxue Huayu drugs.In recent years,Xuebijing injection in clinic gradually used in the treatment of sepsis,and achieved good effect.The effect of Xuebijing injection in the treatment of sepsis literature gradually increased,many of which are randomized trial of Xuebijing injection in the treatment of sepsis,but few multi center,large sample randomized controlled trials reports,therefore,this study conducted a meta-analysis through to the domestic and foreign related Xuebijing injection in the treatment of sepsis the therapeutic effects of Xuebijing on,to further clarify the effect of sepsis.MethodsDefining a language for Chinese or English,Chinese term is defined as"Xuebijing" and "sepsis",search Chinese biomedical databases(CBM,1978-2013.09),Chinese journal full text database(CNKI,1980-2013.09)and Chinese Technology Journal Full-text Database(VIP,1989-2013.09).English retrieval words including "XUEBIJING","sepsis","randomized controlled trials","clinical trials" as the search word search of the Cochrane library,Pubmed and EMbase,document retrieval time is a database to 2013 September.By reading the title,abstract and full text and controls the inclusion and exclusion criteria will be selected in accordance with the terms of the randomized clinical trials of literature,to evaluate the selected file provided in accordance with the Cochrane collaboration of randomized controlled trials of simple evaluation method,Cochrane risk bias evaluation tools and Jadad scale,and the following data were extracted from the literature:(1)basic information,such as the first author,published the state and age time,study population;(2)study cases,follow-up time,loss to follow-up,the intervention measures;(3)the clinical indicators:coagulation function evaluation indexes such as platelet count(PLT),prothrombin time(PT)and the activated partial thromboplastin time(APTT),such as white blood cell number index for evaluating the inflammatory response(WBC),C reactive protein(CRP)and TNF-a and clinical evaluation of prognosis of ICU stay,mechanical ventilation time.Results1.Search results1.1 Meta Analysis of Xuebijing injection in treating patients with sepsissurvival conditions MetaFinally 18 articles were included in accordance with the conditions of completely randomized controlled trials published from 2007 to 2013,published time,1172 patients were included in the treatment group,596 people,576 in the control group,group study author and study are from mainland Chinese.1.2 Meta analysis of different doses of Xuebijing Injection on the survival Ditto1.3 The influence of Xuebijing Injection on blood coagulation in patients with sepsisIn the 9 article,in literature regarding the diagnosis of sepsis were the 2001 International Conference on sepsis standard;the time span from 2009 to 2012,3 of them in 2009,2010,2011 2,2012 2;a total sample size of 562 people,the experimental group 283 people,among them 100ml/d group 182,200ml/d group 101;the control group sample size of 279 people,among them 100ml/d sub group 181,200ml/d group 279.According to the daily dose divided into subgroup 100ml/d and subgroup 200ml/d,of which 1 articles about the dose is placed in group 100ml/d 50ml/12h,of which 1 articles about the dose is classified as group 200ml/d 100ml/12h..1.4 Meta Analysis of of Xuebijing Injection on inflammatory markers in patients with sepsis20 randomized controlled trials were included in the literature,such as patients,1082 cases of sepsis,the test group and the control group of 555 cases and 527 cases respectively.These cases can be divided into two subgroups,respectively,100ml/d group and 200ml/d group,the Liu Xuefeng(2010)studies of 50ml/12h in the 100ml/d subgroup,Jiang Baohu(2009)of 100ml/12h in 200ml/d subgroup.1.5 Meta Analysis of Xuebijing injection and ulinastatin synergistic effectA total of 10 literatures were included,7 articles for the study of the 2 arms,3 for the study of the 4 arm,reported the hospitalization time literature 6 articles,reports the mechanical ventilation time literature 4 articles,6 articles reporting APACHE II score;893 people were included,with 212 in the control group Xuebijing group,160 people,158 people of ulinastatin group,ulinastatin and Xuebijing combined treatment group 363.2.The results of Meta analysis Analysis2.1 Xuebijing injection in the treatment of patients with sepsis survival conditions MetaSubgroup 100ml/d:using fixed effect model,Meta analysis showed RD=0.14,95%confidence interval(CI)[0.09,0.19](Test for overall effect:Z=5.05(P<0.00001))of Xuebijing group than in the control group,the survival rate increased by 14%,and there is statistical significance.200ml/d groups:the fixed effect model was used for analysis of Meta RD=0.19[0.09,0.29](P<0.0002),that of Xuebijing group survival rate increased by 19%compared with the control,the difference was significant existence.Two sub associations:the fixed effect model was used for analysis of Meta RD=0.16[0.11,0.21](P<0.00001),namely Xuebijing group than in the control group,the survival rate increased by 16%,and the difference was statistically significant.Publication bias test:according to the Begg rank correlation test and Egger linear regression test were Pr>|z|=0.669 and Pr>|z|=0.45,shows no evidence of publication bias,and the funnel plot symmetry,suggesting no publication bias.2.2 Meta analysis of different doses of Xuebijing Injection on the survival Using Bayesian network Meta analysis:100ml/d Xuebijing group vs 200ml/d Xuebijing group OR=1.1056,95%CI[0.5147,2.0152]1,or 100ml/d had no statistically significant difference between group 200ml/d and Xuebijing group xuebijing.2.3 The influence of Xuebijing Injection on blood coagulation in patients with sepsis in Meta Analysis of the influence of Xuebijing Injection on platelet2.3.1 Meta Analysis of effect of Xuebijing Injection on PLT in patients with sepsis100ml/d subgroup heterogeneity test I2=71%>50%,significant heterogeneity;the random effect model of Meta analysis to SMD=-0.82,i.e.100ml/d Xuebijing group can decrease sepsis patients PT more than the control group,95%confidence interval[-1.23,-0.41]does not include the 0 and Z=7.40(P<0.00001),the difference between the two groups had statistical significance.200ml/d subgroup heterogeneity test I2=45%<50%,although there is heterogeneity,the heterogeneity of less than 50%,so the fixed effect model of Meta analysis SMD=-0.56,200ml/d subgroups in the decrease of PT in patients with sepsis has more advantages,95%confidence interval[-0.88,-0.24]does not include 0 and Z=3.40(P=0.0007),which shows the significant difference between the two groups.Two sub associations:heterogeneity test I2=63%,random effect model was selected after the merger of SMD=-0.78,namely Xuebijing group compared with the control group in the improvement of PT have more advantages,95%confidence interval[-1.09,-0.47]does not include the 0,shows that there is significant difference between two groups.The two subgroup heterogeneity:heterogeneity test I2=0%,which is between the two groups no significant heterogeneity.2.3.2 Meta Analysis of effect of Xuebijing Injection on PT in patients with sepsis100ml/d subgroup heterogeneity test I2=71%>50%,significant heterogeneity;the random effect model of Meta analysis to SMD=-0.82,i.e.100ml/d Xuebijing group can decrease sepsis patients PT more than the control group,95%confidence interval[-1.23,-0.41]does not include the 0 and Z=7.40(P<0.00001),the difference between the two groups had statistical significance.200ml/d subgroup heterogeneity test I2=45%<50%,although there is heterogeneity,the heterogeneity of less than 50%,so the fixed effect model of Meta analysis SMD=-0.56,200ml/d subgroups in the decrease of PT in patients with sepsis has more advantages,95%confidence interval[-0.88,-0.24]does not include 0 and Z=3.40(P=0.0007),which shows the significant difference between the two groups.Two sub associations:after heterogeneity test I2=63%,random effect model was selected after the merger of SMD=-0.78,namely Xuebijing group compared with the control group in the improvement of PT have more advantages,95%confidence interval[-1.09,-0.47]does not include the 0,the difference between the two groups has statistically significance.Test for heterogeneity between the two subgroups:the test for heterogeneity of I2=0%,which is between the two groups no significant heterogeneity.2.3.3 Meta Analysis of effect of Xuebijing Injection on APTT in patients with sepsis100ml/d subgroups:heterogeneity test I2 = 0%,the within group study does not exist between the heterogeneity,the fixed effect model of Meta analysis SMD=-0.76,95%confidence interval[-0.97,-0.55]does not include 0,namely 100ml/d Xuebijing group compared with the control group in the improvement of APTT in patients with sepsis more advantages.200ml/d subgroup:heterogeneity test I2= 5%<50%,therefore also use fixed effect model to SMD=-0.88,95%confidence interval[-1.21,-0.55]does not include the 0,and Z=5.20(P<0.00001),indicating that 200ml/d Xuebijing group compared with the control group improved more in patients with sepsis in PT.Two sub associations:heterogeneity test I2=0%,description of each study group was not obvious heterogeneity,so the fixed effect model was used for analysis of Meta SMD=-0.79,95%confidence interval[-0.97,-0.61]does not include the 0 and Z=8.66(P<0.00001),that of Xuebijing group compared to the control group in the improvement of sepsis in this PT more favorable aspects.Test for heterogeneity between the two subgroups:two sub formation heterogeneity I2=0%,shows obvious heterogeneity does not exist two subgroups.2.3.4 Meta Analysis of effect of Xuebijing Injection on TT in patients with sepsis100ml/d subgroups:heterogeneity test I2=7%<50%,although each study heterogeneity,but heterogeneity significantly smaller,so the fixed effect model of Meta analysis SMD=-0.65,95%confidence interval[-0.89,-0.41]does not include the 0 and Z=5.31(P<0.00001),Xuebijing group than that of 100ml/d the control group in improving TT more advantages.200ml/d subgroups:heterogeneity test I2=66%>50%,significant heterogeneity;the random effect model of Meta analysis SMD=-0.99,95%confidence interval[-1.70,-0.29]and Z=2.76(P=0.006),namely 200ml/d Xuebijing group than the control group can improve TT in patients with sepsis.Two sub associations:heterogeneity of I2=37%<50%,fixed effects model was used to SMD=-0.69,95%confidence interval[-0.89,-0.50]and Z=7.01(P<0.00001),namely Xuebijing group benefits for patients with sepsis in the improvement of PT more.Two subgroup heterogeneity between I2=0%,shows obvious heterogeneity does not exist two subgroups.2.4 Meta Analysis of Xuebijing Injection on inflammatory markers in patients with sepsis2.4.1 Meta Analysis of Xuebijing on white blood cells of patients with sepsis(WBC)analysis of the impact of the number100ml/d subgroups:heterogeneity test I2=6%<50%,can think of no significant heterogeneity,the fixed effect model of WMD=-2.81[-3.32,-2.29],the confidence interval does not include 0,that of Xuebijing group compared with the control group there were significant differences,namely Xuebijing group and the test group,the number of more can improve WBC.200ml/d subgroups:heterogeneity test I2=7%<50%,can think of no significant heterogeneity,the fixed effect model of WMD=-3.06[-3.74,-2.37],,the confidence interval does not include 0,that of Xuebijing group compared with the control group had significant difference in the number,Xuebijing group than the control group improved more in WBC.Two sub assemblages and the test for heterogeneity:I2=0%,the compare between studies there is no statistical heterogeneity,fixed effects model was used to WMD=-3.06,the 95%confidence interval[-3.74,-2.37]does not include the 0,and Z=8.76(P<0.00001),illustrated combined blood will net group compared with the control group,Xuebijing group in sepsis patients improve WBC number is more favorable,and there was significant difference.The two subgroup heterogeneity between subgroups:two heterogeneity between I2=0%,shows obvious heterogeneity does not exist two subgroups.Publication bias test:using funnel Tufade basic symmetric figure,and according to the Begg rank correlation test and Egger linear regression test were Pr>|z|=0.152 and Pr>|t|=0.126,showed no evidence of publication bias.2.4.2 Meta Analysis of Xuebijing Injection on patients with sepsis procalcitonin(PCT)to analyse the effect100ml/d group:only one paper,SMD=-2.82,the 95%confidence interval CI,[-3.44,-2.19]200ml/d subgroups:heterogeneity test I2=86%,far greater than 50%,the random effect model with SMD=-1.37,the 95%confidence interval CI,[-1.80,-0.95]does not include the 0 and Z=6.36(P<0.00001),as compared with the control group,in PCT group is more favorable to the improvement in Xuebijing patients with sepsis,and the difference is statistically significant.Two and after:heterogeneity test I2=90%,the random effect model with SMD=-1.82[-2.18,-1.47]and Z=10.20(P<0.00001),namely after the merger,the comparison between the two groups,Xuebijing group has more advantages in improving PCT in patients with sepsis,two group of comparison difference different statistical significance.The two subgroup heterogeneity:heterogeneity test I2=92.9%,indicating that two groups has statistical heterogeneity.2.4.3 Meta analysis of the effects of Xuebijing on c-reactive protein in patients with sepsis100ml/d subgroups:heterogeneity test I2=80%,the effect of model SMD=-1.05,and its 95%confidence interval CI,[-1.59,-0.51]does not include the 0 and Z = 3.80(P=0.0001),namely that Xuebijing group than in the control group in reducing the body pathological CRP compared with the control group more benefits,and there was significant difference between two groups.200ml/d subgroups:heterogeneity test I2=75%,the random effect model of-1.53[-2.10,-0.97],because of the confidence interval does not include 0 and Z=5.32(P<0.00001),so that the Xuebijing group could improve the pathological CRP increased more than that of the control group,and between the two groups of different than the poor statistically significant.Two and after:heterogeneity test I2=79%,the random effect model of SMD=-1.30,the 95%confidence interval[-1.71,-0.90]and Z=6.29(P<0.00001),as compared with the control group,Xuebijing group to reduce patient pathological CRP ability is stronger,and the two group was statistically significant compared with.The two subgroup heterogeneity:heterogeneity test I2=88.3%,indicating that two groups has statistical heterogeneity.Publication bias analysis:according to the Begg rank correlation test and Egger linear regression test were Pr>|z|=0.008 and Pr>|t|=0.015,showed the presence of publication bias,and the funnel plot asymmetry also supports this result.2.4.4 Meta analysis of the effects of Xuebijing on on tumor necrosis factor a in patients with sepsis100ml/d subgroups:heterogeneity test I2=96%,far greater than 50%,using a random effects model analysis of Meta SMD=-1.46,the 95%confidence interval[-1.83,-1.10]does not contain 0 and Z=7.93(P<0.0001),namely Xuebijing group in the reduction of tumor necrosis factor alpha group has more advantages than and the difference between the two groups,compared with statistical significance.200ml/d subgroups:heterogeneity test I2=90%,much greater than 50%,using a random effects model analysis of Meta SMD=-1.35,the 95%confidence interval[-1.57,-1.12does not contain 0 and Z=11.75(P<0.0001),namely Xuebijing group in the reduction of tumor necrosis factor alpha aspects than controls more advantage,and differences between the two groups was statistically significant.Two and after:heterogeneity test I2=92%,by using a random effects model analysis of Meta SMD=-1.38[-1.57,-1.19],because of the confidence interval does not include 0 and Z=14.1(P<0.0001),so you can think of Xuebijing group compared with the control group improved more in patients with sepsis inflammatory factor TNF-a level,with statistical significance and the difference between the two groups.The two subgroup heterogeneity:heterogeneity test I2=0%,description of statistical heterogeneity does not exist between the two groups.Publication bias analysis:Egger linear regression test was Pr>|z| = 1.000 and Pr>|t| =0.889,and the funnel plot supports this result,so the existence of publication bias.2.4.5 Meta analysis of the effects of Xuebijing on Interleukin-6(IL-6)in patients with sepsis100ml/d subgroups:heterogeneity test I2=96%,far greater than 50%,using a random effects model analysis of Meta SMD=-2.20,the 95%confidence interval[-3.69,-0.91]does not contain 0 and Z=3.25(P = 0.001),namely Xuebijing group in reducing the IL-6 has more advantages than the control group,and the difference between the two groups with statistical significance.200ml/d subgroups:heterogeneity test I2=94%,much greater than 50%,using a random effects model analysis of Meta SMD=-1.71,the 95%confidence interval[-2.80,-0.61]does not contain 0 and Z=3.06(P = 0.002),namely Xuebijing group in reducing the IL-6 has more advantages than the control group,and the difference comparison of the two groups was statistically significant.Two and after:heterogeneity test I2=95%,by using a random effects model analysis of Meta SMD=-1.97[-2.78,-1.16],because of the confidence interval does not include 0 and Z=4.74(P<0.00001),so you can think of Xuebijing group compared with the control group improved more in sepsis patients.Factor IL-6 levels,and has significant difference between the two groups.The two subgroup heterogeneity:heterogeneity test I2=0%,description of statistical heterogeneity does not exist between the two groups.Publication bias analysis:the funnel plot asymmetry,and according to the Begg rank correlation test and Egger linear regression test were Pr>|z|=0.008 and Pr>|t|=0.002,and the funnel plot also supports this result,show the presence of publication bias.2.5 Meta analysis of synergistic effect of Xuebijing injection and ulinastatin2.5.1 Meta analysis of Xuebijing injection and ulinastatin cooperative to shorten the time of mechanical ventilation in patients with sepsisThere are 3 reports the duration of mechanical ventilation patients,included 297 patients with sepsis patients,including 41 cases in the control group,63 cases of Xuebijing group,ulinastatin group 92 cases,Xuebijing combined with ulinastatin combined treatment group of 101 cases.After 50000 iterations,the first 10000 for return to remove the effect of initial value,after 40000 times for sampling,the final results as below,totresdev =8.1101 and the total number of arms in 10 very close,so the internal stability.Figure diff[A,B]A and B comparison of the WMD value,namely A group than in the B group mechanical ventilation time WMD days.In Figure 1,2,3,4 respectively refer to the control group,Xuebijing group,ulinastatin group and Xuebijing combined with ulinastatin treatment group,so if diff[1,2]-8.0056(days),95%confidence interval[5.5666,10.2702],control group and Xuebijing group length of hospitalization(days 8.1101),because of the confidence interval does not include 0,which shows the significant dififerences between the two groups;diff[2,3]=-1.8122,95%confidence interval is[-3.5987,0.1659],illustrate the Xuebijing group and ulinastatin group mechanical ventilation time to short-1.8122(days),but the 95%confidence interval of CI includes 0,two group differences,but not significant;the other is by analogy,see table.2.5.1 Meta analysis of Xuebijing injection and ulinastatin collaborative shortened ICU in patients with sepsis hospitalization timeThe included papers have 5 reports the hospitalization time of sepsis in patients with sepsis,543 people,the data call in the R software software for analysis of Bayesian network Meta.After 50000 iterations,the first 10000 for return to remove the effect of initial value,after 40000 times for sampling,the final results as below,totresdev =12.5262 and the total number of arms in 14 very close,so the internal stability.Figure diff[A,B]A and B comparison of the WMD value,namely A group than in the B group,length of hospital stay WMD days.In Figure 1,2,3,4 respectively refer to the control group,Xuebijing group,ulinastatin group and Xuebijing combined with ulinastatin treatment group,so if diff[1,2]=9.4730(days),95%confidence interval CI,[7.8710,11.0797],control group and Xuebijing group length of hospitalization(days 9.4730),because of the confidence interval does not include 0,which shows the significant differences between the two groups;difft2,3]=-1.2283,95%confidence interval[-3.0343,0.8166]included 0,that of Xuebijing group and ulinastatin group were shorter hospitalization time(1.2283 days),the differences in the two groups,but not statistical significance;the other is by analogy;see table.The above document in the R software package called nlme,was obtained as shown,the results and the same,the result is relatively stable.Conclusions1.Xuebijing can improve the survival rate of patients with sepsis;2.Both Xuebijing injection of 200ml/d and 100ml/d,and there are no significant increased survival rate;3.Both 100ml/d Xuebijing injection and Xuebijing injection can improve PLT number and disincrease the number of pathological PT,APTT,TT;4.Both 100ml/d Xuebijing injection or 200ml/d can improve the sepsis patients white blood cell trees and disincrease procalcitonin(PCT),C reactive protein(CRP),TNF-α and interleukin-6(IL-6)level;5.Xuebijing injection and Ulinastatin Injection synergistic effect to shorten the duration of mechanical ventilation:A)Single group Xuebijing group and control,can shorten the duration of mechanical ventilation;B)With ulinastatin group Ulinastatin group and control,can shorten the duration of mechanical ventilation;C)Single Xuebijing group and ulinastatin group,can shorten the mechanical ventilation time,but the difference was not statistically significant;D)Xuebijing combined with ulinastatin used than single Xuebijing group and ulinastatin group can shorten the time of mechanical ventilation in patients with.6.Xuebijing injection and Ulinastatin Injection synergistic effect shorten the length of stay in ICU:E)Single group Xuebijing group and control,can shorten the length of stay in ICU;F)With ulinastatin group Ulinastatin group and control,can shorten the time of ICU;G)Single Xuebijing group and ulinastatin group,can shorten the length of stay in ICU,but the difference was not statistically significant;H)Xuebijing combined with ulinastatin used than single Xuebijing group andulinastatin group can shrink ICU stay in patients with 5 short. |
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