Clinical Research Of Continuous Blood Purification In Improving The Immune Function And Prognosis Of Severe Sepsis Patients

Objective: Being one of the major causes that result in the death of critical patients,the severe sepsis incidence is very high in ICU.Excessive inflammatory reaction was observed in the early phase of severe sepsis,mass of inflammatory mediators were secreted,but inflammatory-targeted treatment proved to be unefficacious in the clinic.Studies have confirmed new inflammatory meditors exist in late period of inflammation: HMGB1(High- mobility group box 1 protein),and HMGB1-targeted intervention widened the therapeutic window.In the late period of severe sepsis,the body is in a state of immune paralysis,the impairement of lymphocyte proliferation ability and apotosis of mass lymphocyte were observed,and thus increased the suscep- tibility to pathogens.According to current studies,the HLA-DR(human leukoyte Antigen DR) expression level on CD14+ monoctye can reflect host’s immune state.Hemofitration is one of the important treatment measures of severe sepsis.In this study, hemofitration was performed to treat severe sepsis,and serum HMGB 1,HLA- DR level were monitored to investigate the improvement of the inflammatory meditors’ clearance ability,immune function and prognosis of blood purification on severe sepsis patients.Methods: 40 severe sepsis patients admitted in the ICU of Xingtai people’s hospital from Jan.2014 to Dec 2014,and they were divided into two groups according to different treatments,Group A(General treatment group,n =20)received general treatment according to the severe sepsis treatment guideline of 2012;Group B(general treatment in combination with blood purification group,n=20)received 72 hours’ blood purification in base of general treatment.And serum creatinine level,APACHE Ⅱ(Acute Physio- logical and Chronic Health Evaluation)and SOFA(Sequential Organ Failure Assesment) were recorded.The HMGB1 level was measured by ELISA,the peripheral blood HLA-DR expression level was detected using flow cytometry and the prognosis was evaluated after 28-day follow–up.In addition,we enrolled 10 healthy volunteers as control group,whose serum HMGB1、HLA-DR level were recorded.The differences between each group were statistically significant, indicating that application of continuous blood purification for the treatment of severe sepsis patients with severe sepsis can reduce inflammatory reaction extent, improve immune function and improve prognosis and reduce mortality.Results:1 Compare the severe sepsis patients with healthy volunteersCompare to the healthy volunteers,the serum HMGB1 level of severe sepsis patients increased,while the HLA-DR expression level decreased, the difference was statistically significant(P<0.01).2 Compare the HMGB1 level in general treatment group and the group with the combination blood purificationHMGB1 reached up to the peak at T1 and began to decline at T2, In general treatment group the differences between T3 and T0 time point were statistically significant(P<0.5),the differences between T2 and T0 time point were no statistically significant(P>0.5), In the patients of the group with the combination of blood purification,there was statistical significance between T2、T3 and T0(P<0.05).Compared two groups, the blood HMGB1 level of the patients have statistical significance between T2 and T3(P<0.05).HMGB1 could be detected in the ultrafiltrate.3 Compare the HLA-DR level in general treatment group and the group with the combination of blood purificationIn the patients of the general treatment group.,the HLA-DR expression rate was lowest at T1,and then raised gradually,but there was no statistical difference between T2、T3and T0(P>0.05).In the patients of the group with the combination of blood purification.the serum HLA-DR expression rate raised gradually,and there was statistical difference between T2、T3 and T0(P<0.05).The HLA-DR expression rate was markedly higher than that of general treatment group,and there was statistical difference at T2、T3(P<0.05).4 Compare the blood creatinine and lactate level in the general treatment group and group with treatment combined with blood purificationIn general treatment,the patients’ blood creatinine reached up to the peak at T1 and began to decline at T2, but there was no statistical between T2、T3 and T0 time points(P>0.05);lactate level declined gradually,,the difference of the serum lactate level between T2、T3 and T0 was statistically significant(P<0.05).In the patients with treatment combined with blood purification,the serum creatinine and lactate level declined gradually,and the differences between T1、T2、T3 and T0 points were statistically significant.(P<0.05).Compare the serum creatinine level in the above two groups,we found statistical difference at T1、T2、T3 point(P<0.05);as to the lactate level,there was statistical difference at T1(P<0.05).5 Compare the changes of APACHE II score and SOFA score in general treatment group and the group with combination with blood purification groupIn general treatment group,the APACHEII score,SOFA score declined gradually,and the differences of APACHEII score were statistically significantly between T3 and T0 points(P<0.05),no statistical difference was observed in SOFA score at each time points(P>0.05).In the group combined with blood purification,APACHEII score, SOFA score declined gradually, and the differences of APACHEII score were statistically significantly between T2、T3 and T0 points(P<0.05),. SOFA score also presented trend of decline,but there was no statistical difference(P>0.05).In the comparison of two groups,we found that there was statistical significance in APACHEII score at T3,and no statistical difference in SOFA score at each time points.6 Compare the outcome after 28 days’ treatment in the general treatment group and the group with combination treatment groupIn group A,6 patients died,14 patients survived with a mortality of 30%;In group B,4 patients died,16 patients survived,and the mortality was 20%, the difference of mortality was statistical significance(P<0.05),indicating that the application of blood purification for severe sepsis can improve its prognosis.Conclusion:1 Excessive inflammatory reaction and immunosuppression exist in sever sepsis,serum HMGB1 is markedly increased and HLA- DR expression rate is decreased obviously,patients with continuous high HMGB1 and low HLA-DR have bad prognosis.2 CVVH treatment can remove part of serum HMGB1 in severe sepsis patients through convention continuously,thereby weakening the the plasma HMGB1 peak concentration.3 CVVH treatment can promote HLA-DR expression, regulate the body’s immune function, so as to improve patients’ immune function.4 CVVH treatment can improve the severe patients’ renal function remove lactic and maintain the body’s internal environment.5 CVVH treatment can reduce the mortality of severe sepsis patient,improve the prognosis,and thus performs as one of the important methods of severe sepsis therapy.