Sepsis refers to the disorder of the body's response to infection and causes organ dysfunction that can threaten the body(16),Sepsis affects almost every organ system. The management of sepsis depends on early recognition and empirical antimicrobial treatment, fluid resuscitation and vasopressin treatment(17,18). At present, there is no gold standard for diagnosis of sepsis, which is extremely challenging for its diagnosis and is one of the most important causes of death in the world. More than 30 million people are diagnosed with sepsis each year, and 5 million of them die. Even if the condition is relieved, many patients have long-term sequelae, which requires long-term care and brings a great burden to society and families. The World Health Assembly and WHO in 2017 make sepsis a global health priority(19). Although the global trend of sepsis reduction has been shown, it is important that there are still huge differences in the total number of sepsis between regions. Early diagnosis and early treatment are meaningful for improving patient prognosis and reducing mortality. Therefore, we hope to find simple and cheap diagnostic criteria(15,19).
In this study, 499 patients and 96 healthy individuals were included, and were divided into sepsis group (n = 300), SIRS group (n = 151), infection group (n = 48), and control group(n = 96) using diagnostic criteria for bacterial infection, systemic inflammatory response syndrome and Sepsis2.0 diagnostic criteria. Kruskal-Wallis test was used to compare NE, WBC, D-Dimer, PT, CRP, PCT and IL-6, and ROC curve was drawn to evaluate the diagnostic efficacy of parameters.
PCT, IL-6, and CRP have always played an important role in the early diagnosis, disease evaluation and prognosis judgment of sepsis(20,21). However, CRP and PCT are both inconsistent in their diagnostic capabilities(22). CRP has been widely studied for sepsis. Its diagnostic accuracy is called into question because the results are inconsistent and variable depending on the severity of the disease and infection (15). One study suggested that CRP was less sensitive (AUC81, 96% sensitivity, 79% specificity) and less diagnostic value than PCT in sepsis (23). This is consistent with the results of our study, in which PCT was superior to CRP in the diagnosis of sepsis (AUC99.9, sensitivity 97.4%, specificity 100%) compared with healthy controls, which was beneficial to the diagnosis of sepsis. However, there was no statistical significance in the identification of sepsis in the SIRS group and the infection group (P > 0.05). Studies of its diagnostic value have yielded mixed results, a meta-analysis found that the AUC of PCT was 0.85, the sensitivity and specificity of predicting sepsis in critically ill patients were 77% and 79%(24). A retrospective study found that the diagnostic utility of PCT in predicting sepsis was relatively low (15). PCT is clinically used to distinguish infectious sepsis from non-infectious diseases, which is consistent with our study. PCT levels were significantly higher in the sepsis group and other groups than in the healthy controls. However, PCT did not differentiate sepsis from infection or SIRS, which may be related to the diagnostic criteria of sepsis. The prognosis of infection varies, including death, remission, sepsis, etc. It may become a link in the progression to sepsis. SIRS standard and infection were used as the diagnostic criteria for sepsis, so there was no statistical significance in the difference analysis of PCT between the sepsis group and the infection group. For IL-6, a prospective, controlled, multicenter study found that IL-6 can be used as a diagnostic and prognostic biomarker for sepsis and septic shock (21), IL-6 is a better diagnostic indicator of sepsis than PCT and CRP(21). It was also suggested that the diagnostic value of IL-6 in patients with sepsis was almost equal to that of PCT. A meta-analysis suggested that IL-6 should be used as an adjunctive diagnosis in patients with non-infectious inflammation rather than as a diagnostic indicator(22). There are also studies suggesting that the diagnostic value of PCT is better than IL-6 (AUC59.6, sensitivity 43.6%, specificity 100%). In this study, the sepsis group and the healthy control group have the same results (AUC98. 1, P < 0.05). Considering that there are 283 mixed infection patients in the sepsis group, it may be related to the patient's severe illness and impaired immune function. However, when sepsis is compared with the other two groups, it shows a certain differential diagnosis significance, which can be used as a tool to identify sepsis, which is conducive to early targeted sepsis bundle therapy to improve prognosis.
In addition, we also found that TBIL was significantly different in sepsis compared with infection or healthy controls, and showed certain diagnostic value. Given that hyperbilirubinemia is a common complication of sepsis, it is used as an indicator of liver function in APA CHEII and sequential organ failure scores (8), which is associated with poor prognosis of sepsis - associated liver injury (25). Some studies also believe that although TBIL is higher in the sepsis group, its correlation is not clinically significant because it is a parameter of the SOPA standard(26). Our study did not adopt the SOPA standard, TBIL still showed differences between groups, and comparing the sepsis group and the infection group, the AUC of TBIL was 60.0, the sensitivity was 55.3%, and the specificity was 64.6%, which is meaningful for differential diagnosis. Therefore, it is believed that it may be beneficial to early diagnosis.
Unlike other sepsis biomarkers such as PCT or CRP, WBC, NE, and D-dimer are the first laboratory test results that clinicians can use. Therefore, we analyzed the diagnostic value of NE, WBC and D-dimer and evaluated their applicability as early diagnosis of sepsis patients. In our study, WBC, IL-6, NE, TBIL showed statistical differences in the comparison between the sepsis group and the infection group. The AUC of NE was 67.6, the largest of the four, with the highest specificity (95.8%) but the lowest sensitivity (49%). The sensitivity and specificity of WBC (AUC66.7) were 51% and 89.6%, and both NE and WBC had certain value of differential diagnosis, although their performance was general. The study suggested that the leucocyte, NE value increased gradually according to the severity of the infection (27). The diagnostic accuracy of total leukocyte parameters can provide valuable information for the diagnosis and follow-up of sepsis in patients with liver damage in ICU. Neutrophil dysfunction may actively participate in the development of sepsis (27). In our study, both NE and WBC in the sepsis group and the healthy control group showed diagnostic significance, and the diagnostic efficiency was fair (NE: AUC86.5, sensitivity 79.5%, specificity 100%; WBC: AUC77.9, sensitivity 66.7%, specificity 100%). The lack of statistical significance in the comparison between the sepsis group and the SIRS group is related to our use of the Sepsis2.0 diagnostic criteria. prospective cohort study of early biomarkers of sepsis in burn patients: NE can be used as a biomarker for predicting/early diagnosing sepsis. The use of therapeutic interventions for neutrophil dysfunction may reduce the incidence of nosocomial infection and sepsis after burns. The study suggests that the total number of white blood cells (p < 0.05) in patients with sepsis is higher than that in the control group, which is consistent with our analysis. There is no statistical difference in platelets between the control group and sepsis patients, which may be related to the impact of their choice of lung disease as the control group on the results (28,29). In our data analysis, although PLT is statistically different in the comparison between the sepsis group and the healthy control group (P < 0.05), it has no diagnostic value. In the comparison between the sepsis group and the SIRS group reflect a certain significance of differential diagnosis and can be used as an auxiliary indicator. A study of ICU patients with liver disease showed that it was related to significant differences in WBC and CRP. The diagnostic accuracy of white blood cell parameters may provide valuable information for the diagnosis and follow-up of sepsis in ICU patients (especially patients with liver dysfunction) (27). There are also many studies suggesting that the combination of white blood cell count or neutrophil count with other indicators may increase the detection rate of sepsis, which can guide us in the next step of research (14).
D-dimer is a fibrin degradation product, and the increase of D-dimer level indicates the presence of hypercoagulable state and secondary fibrinolysis in the body. Many factors can increase it, such as infection, DIC, heart or kidney damage, thrombolytic therapy, etc. Sepsis is a clinical syndrome that complicates severe infections. It is characterized by the main manifestations of inflammation (vasodilation, white blood cell accumulation, increased vascular permeability, etc.) appearing in tissues far away from the infection site (30). Inflammation and clotting affect each other, Studies have shown that clotting can be activated by inflammation, which leads to endothelial damage and the formation of exudative platelet aggregation (28). In our study, D-dimer showed excellent diagnostic value in the sepsis group, and we believed that D-dimer, PCT and CRP were all conducive to the early detection of sepsis. In one study of mice(28), a sepsis model was created by intraperitoneal injection of liposolysaccharide (LPS). 24 hours later, there was an exudative platelet aggregation in the liver, and the levels of AST, ALT, and DBIL were significantly elevated. This study suggests that Neutrophil Extracellular Traps (NETs) formation and platelet aggregation are the first steps in the development of liver dysfunction in sepsis. Inflammation and coagulation play a key role in the pathogenesis of septicemia, leading to multi-organ failure, echoing Sepsis3.0 diagnostic criteria.