| 1.BackgroudSepsis is still a major problem in the world.It is a common disease in the ICU ward.It has the characteristics of high mortality,difficult treatment and rapid progress.It is also a common reason for patients to stay in ICU days,increase mechanical ventilation time and increase the cost of treatment.At present,there are many advances in the research of sepsis,but the mechanism of its pathogenesis and disease changes is very complex.At present,the treatment of sepsis has made little progress.There is no unified standard for clinical diagnosis of sepsis in the past,With the deepening of our research on sepsis and the further understanding of the pathophysiology of sepsis and clinical data analysis.The third sepsis consensus proposed the definition and diagnostic criteria of sepsis and septic shock of the new,published in the February 2016 Journal of the American Medical Association,which for clinicians to timely discover and provide the basis for the treatment of sepsis,also can regulate the diagnosis and treatment of sepsis.Many previous studies suggest that sepsis is an excessive inflammatory response that causes organ dysfunction in patients and then progresses to multiple organ failure,But with a lot of research,we have found that the immune state of patients with sepsis is not always in the stage of excessive inflammation,On the contrary,the study of many dead patients showed that most of the immune state of the patient was in severe immune function inhibition,The issue of this argument has prompted many people to reunderstand the pathophysiological process in the development of sepsis.Richard S.Hotchkiss and others found that the immune function of sepsis patients changed with time.Although in early stage of sepsis,both the proinflammatory and anti-inflammatory reactions were activated,but the inflammatory reaction was dominant.But in the past 20 years,we can not reduce the mortality of patients by using the method of inhibiting inflammation patients,and clinical trials failed to remind us that patients with sepsis"sustained inflammation"argument is wrong or incompleteWith the progress of sepsis,the anti inflammatory reaction is dominant,and it is in this stage that secondary double infection and reactivation of the virus will occur.Sepsis due to cytokine storm is the cause of death in early stage of inflammatory reaction,and the late death cases are due to the inhibition of immune function and resistance to pathogens.Immune function has a huge impact on the prognosis of sepsis patients.The relationship between immune function and prognosis of patients with sepsis has also become a research hotspot in critical care medicine.Many basic studies have found that the changes in the immune function of patients with sepsis are closely related to the change of the patient’s condition and the prognosis.But at present,the clinical research on immune function and prognosis of sepsis patients is very rare,mainly for lack of a unified diagnostic criteria for clinical immune function.Many studies take serum samples from death patients and further study the immune function and quantity of the patients to determine the immune status of the patients at that time.In clinic,the method of judging the state of immune function in basic experiment is difficult to implement.At present,there is a clinical application of HLA-DR/CD14 ratio to monitor the immune function of sepsis patients.However,its clinical value is not uniform.Recently,Anne M.Drewry,MD et al study published in the Journal Shock shows that the absolute value of lymphocyte in critically ill patients is less than 1.2*10~9/L,and continued for 4 days,the immune function in the inhibitory state,the prognosis of the patients with poor outcomes,and the results with independent monitoring of B lymphocytes,T lymphocytes and T/B lymphocytes had no significant difference.But there are no related clinical reports.Studies have shown that immunosuppression induced by sepsis has an important characteristic,which is the reduction of lymphocytes,including CD4 and CD8 Thunb,and follicular dendritic cells through apoptosis.A growing body of evidence suggests,Sepsis patients are accompanied by lymphocyte decline at the time of diagnosis,and can continue until 28days.Some studies of BT T lymphocytes show that death occurs on the third day compared with surviving sepsis patients.On day 7,lymphocytes were significantly reduced.Heffernan et al.Found that in patients with trauma,it lasted for 4 days.The absolute value of lymphocyte in patients with low mortality rates were significantly higher than that in normal lymphocytes,and sustained and continued low absolute value of lymphocyte immune suppression related.Anne MD et al,Drewry recently,research published in the Journal Shock shows that,when the absolute value of lymphocyte in sepsis patients less than 1.2*109/L and continued for 4 days when the 28day mortality and 1 year mortality rate increased significantly,the probability was significantly higher than the absolute value of lymphocyte in normal group two secondary infection pathogenic bacteria infection and opportunity.Therefore,they think,suffering from sepsis Lymphocytopenia is a biomarker of immunosuppression induced by sepsis.We know that the immune function is closely related to the prognosis of the patients,but there are few reports in the clinical aspects.This is because of the monitoring of the number of T lymphocyte subsets in the patients.HLA-DR expression in neutrophils,It is very difficult for clinical work to monitor the immune function of patients by LPS-induced tumor necrosis factor-α.To judge the immune function of patients by monitoring the absolute value of lymphocytes by blood routine.It’s easy to achieve clinically,It is less difficult to operate,so we use this standard to judge sepsis.In order to evaluate the prognosis of patients with sepsis and identify the critically ill patients,it is better to explore the influence of the changes of immune function caused by persistent lymphocytopenia on the prognosis of patients with sepsis.2.ObjectivesThe immune function of patients with sepsis was evaluated by continuously monitoring the changes of the absolute value of lymphocytes in blood routine,and the immune function of patients with sepsis was judged by lymphocytes for 4 consecutive days before observing the end point.To evaluate the relationship between the initial immune function and the prognosis of sepsis patients,and to explore the relationship between the prognosis of sepsis patients and other factors,and to elucidate the clinical prognosis and other characteristics of sepsis patients.3.Methods3.1 Inclusion criteriaSepsis definition and diagnostic criteria of Sepsis-3 in accordance with the international consensus on diagnosis:host organ dysfunction caused by infection,SOFA score more than 2 points.The circulation failure is diagnosed according to the expert consensus of the emergency clinical practice of acute circulation failure in China.The diagnostic criteria for immunosuppression:the absolute count of lymphocytes in patients was less than 1.2 x 109/L,and lasted for 4 days,which could be judged to be immunosuppressive.3.2 Exclusion criteria(1)the patient was<18 years old,(2)congenital or acquired immunodeficiency disease,(3)the long-term use of glucocorticoids(over 3 months),(4)long term use of immunosuppressive drugs,(5)the tumor patients in the course of chemotherapy and chemotherapy,(6)pregnant women,(7)the time of hospitalization was less than 4 days.3.3 GroupingAccording to the initial immune function state after diagnosis,it was divided into the immune function inhibition group and the normal immune function group.According to the age of 65 years old and equal to the aged group,the patient is less than 65 years old and divided into the young group.According to the initial immunological function and the endpoint of observation,the immune function was divided into continuous inhibition group,continuous normal group,first inhibition normal group and first normal post suppression group.3.4 Data CollectionSOFA score,within 24 hours of the APACHE II score,C reaction to collect patients with sepsis diagnosis protein(CRP)and procalcitonin(PCT),whitebloodcellcount(WBC)andaspartate aminotransferase(AST),alanine aminotransferase(ALT),creatinine(Cr);whether respiratory failure,circulatory failure and whether the use of hormone therapy in the course of(more than 48 hours of continuous use of hormone),whether the use of immunomodulatory drugs(immunomodulatory drugs to thymic peptide five,thymosin,thymalfasin,more than 72 hours of continuous use);high volume hemofiltration treatment is used in the course of sepsis were collected;after 4 consecutive days and observe the end point before the event for 4 consecutive days of absolute value of lymphocyte count.4.Results4.1 Overall situation:In a total of 393 patients with sepsis,202(51.40%)died within 28 days and 219(55.72%)were immunosuppressed.4.2 The outcome of the group was according to the primary immunologic state:The mortality rate of the immune function inhibition group was higher than that of the normal immune function group.(65.30%vs 33.90%,P<0.05).4.3 According to the age subgroup of the patients,the prognosis of the patients was as follows:Under the immunosuppressive condition,the mortality rate of the elderly group was higher than that of the younger group,but there was no statistical difference.(26.30%vs 15.80%,P=0.061);under normal immune conditions,the mortality rate of the elderly group was higher than that of the younger group,and the results were statistically different.(48.20%vs 20.20%,P=0.000).4.4 According to the changes of the immune function state before and after the preliminary end point,the prognosis and related results were as follows:Persistent inhibition group and First normal suppressing group were higher than Continuous normal group,continued after the first inhibited the normal group the mortality rate is high,the difference was statistically significant(P<0.05);and the first normal group and sustained suppression of inhibitory group was no significant difference(P>0.05),the normal group and the first sustained suppression of normal group.There was no statistical difference(P>0.05);we also found that in the initial state for immune suppression conditions,the elderly than young people continue to restrain a higher incidence(74.6%vs 54.30%,P<0.05),while in the initial immune state for normal conditions,the elderly immune inhibition rate than younger high(30%vs 9.60%,P<0.05).6.ConclusionsPatients with persistent lymphopenia are immunosuppressed and have a close relationship with the prognosis of sepsis.The prognosis of patients with combined immunosuppression is poor;patients with sepsis in the elderly are more likely to have immunosuppression,are less likely to recover,and have a worse prognosis than young patients. |
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