| Research backgroundThe sublingual microcirculation imaging system can dynamically monitor microcirculation parameters and evaluate changes in microvascular endothelial glycocalyx thickness through software analysis.After sepsis occurs,early recognition and proper management are key to improving outcomes.Endothelial glycocalyx injury occurs in the early stages of sepsis and is an important mechanism affecting vascular homeostasis.Therefore,it is speculated that monitoring glycocalyx damage indicators has a certain effect on the early diagnosis and prognosis of sepsis.The qSOFA score,a commonly used clinical screening tool,has high specificity but poor sensitivity.Whether combined with glycocalyx damage indicators can improve its diagnostic value remains to be further explored.Microcirculation disturbance is an important cause of organ dysfunction in patients with sepsis and affects prognosis.Screening for appropriate indicators to detect changes in microcirculation and determine its impact on prognosis has become a hot topic in critical care in recent years.Septic shock is an acute and severe circulatory disorder complicated by sepsis.Maintaining hemodynamic stability in the treatment of septic shock is the key to patient prognosis.Fluid resuscitation is the cornerstone of maintaining hemodynamic stability.The end point of resuscitation is the improvement of microcirculatory function.The choice,method,dose,and duration of resuscitation fluids remain to be studied,and inappropriate fluid resuscitation is associated with worse outcomes.The therapeutic effect of different fluid resuscitation on the improvement of microcirculation needs further study.Research purposesThe objectives of this study are to assess the diagnostic accuracy of peripheral blood leukocyte gene expression combined with qSOFA score for early detection of sepsis.Additionally,the study aims to measure the sublingual microcirculatory parameters using an imaging system and evaluate their impact on 28-day mortality in sepsis patients.Moreover,the study intends to compare the changes in microcirculation before and after different resuscitation techniques using a sublingual microcirculation imaging system.The ultimate goal is to identify the most effective resuscitation methods to improve microcirculation function and patient prognosis,providing a foundation for clinical decision-making and future research.Research methodsFifty-eight patients,either with confirmed infections or suspected infections,were categorized into two groups-sepsis group and non-sepsis group based on whether they satisfied the diagnostic criteria of sepsis during the observation period.Furthermore,10 healthy volunteers were selected as the healthy control group.Sublingual microcirculation images were captured by the sublingual microcirculation imaging system within 24 hours of admission in each group to assess PBR.Peripheral blood samples were collected to check related markers of inflammation and glycocalyx damage.Demographic variables,laboratory test results,and physiological parameters were recorded hourly to calculate qSOFA score,NEWS score,and SIRS score.The subjects of this study were patients who received a diagnosis of sepsis in accordance with the Sepsis3.0 criteria upon admission.Sublingual microcirculation evaluations were conducted on these patients at the time of diagnosis,as well as after 12,24,and 48 hours.Clinical data,lab results,and microcirculatory parameters were compared between survivors and non-survivors.The changes in microcirculation indicators at different time points were analyzed,while univariate Cox regression was used to examine the confounding factors that affected patient mortality within 28 days.Additionally,a multi-factor Cox proportional hazard model was employed to analyze how changes in sublingual microcirculation indicators at different time points influenced the early prognosis of patients.A total of 52 patients with septic shock were enrolled in our study.We monitored the change in proportion of perfused small vessels(ΔPPVs)in relation to the 24-hour sublingual microcirculation index and recorded the patients’ 28-day survival status.ROC curve analysis was used to assess the impact ofΔPPVs on patient prognosis,and an optimal cut-off point was determined.Based on this cut-off,patients were divided into two groups:those with improved microcirculation and those without.Clinical data,laboratory test results,and liquid resuscitation methods were compared between the two groups,and a logistic regression model was constructed to examine the effects of different liquid resuscitation methods on patient microcirculation.ResultsAfter using propensity score to match the uneven age distribution,58 patients were retained,including 30 patients with sepsis and 28 patients in the non-sepsis group.At the same time,10 healthy control cases were set up.The diagnostic value of qSOFA(AUC=0.731 95%Cl=0.5999-0.863 P=0.003)was evaluated by ROC curve.The diagnostic sensitivity was 0.533,specificity was 0.929,and Yoden index was 0.462.Kruskal-Wallis test showed that the PBR value of the sepsis group was significantly higher{2.87(2.75-2.96)VS.1.90(1.71-2.04)P=0.000}compared with the healthy control group,indicating that the patients with sepsis had damage to the endothelial glycocalyx.Meanwhile,compared with non-sepsis group,PBR value{2.87(2.75-2.96)VS.2.63(2.35-2.77)P=0.004}was significantly higher in sepsis group.PBR value evaluated by ROC curve showed:PBR(AUC=0.783 95%Cl=0.663-0.903 P=0.000)has certain diagnostic value for sepsis,calculation sample cut-off point of 2.685μm,sensitivity of 0.867,the specificity of 0.643.The PBR value combined with qSOFA score showed that the diagnostic value of PBR+qSOFA(AUC=0.851 95%Cl=0.753-948P=0.000)was improved to a certain extent,with diagnostic sensitivity of 83.3%and specificity of 71.4%.Comparing the AUC results of the two diagnostic methods,the accuracy of qSOFA+PBR diagnosis was better than that of qSOFA diagnosis,and the difference was statistically significant(Z=-2.756 P=0.006).The differences between the groups in glycocalyx damage markers such as Syndecan-1,HS and HA and in inflammation-related proteins such as PCT,IL-6,Caspase-8,Caspase-1,Ik Ba and NARP were also examined.ROC curve test shows that:Syndecan-1(AUC=0.879 95%Cl=0.785-0.972 P=0.000),Caspase-8(AUC=0.687 95%Cl=0.542-0.832 P=0.015),Caspase-1(AUC=0.721 95%Cl=0.583-0.860 P=0.004)and IL-6(AUC=0.663 95%Cl=0.524-0.802P=0.033),which showed a certain predictive value.Compared with the survival group,microcirculation indexes of sepsis patients in the death group were as follows:The proportion of perfusion vessels(small)PPVs decreased significantly,the heterogeneity index HI increased significantly,and PPVs(r=-0.674Rho=0.419 P<0.001),HI(r=0.542 Rho=0.294 P<0.001)were correlated with sequential organ failure score(SOFA).PPVs and HI improved in the survival group over time,but deteriorated in the death group.Multivariate Cox regression analysis showed thatΔPPVs(12h)(RR=0.973 95%CI=0.951-0.997 P=0.025);ΔPPVs(24h)(RR=0.94295%CI=0.915-0.969 P=0.000)had a statistically significant effect on the 28d mortality of sepsis patients.At 12h and 24h,the change rate of sublingual microcirculation standard perfusion vessels had a certain effect on the survival rate of patients,while the effect was not significant at 48h,indicating that the earlier the improvement of microcirculation may be more beneficial to the prognosis of patients.ROC curve test prediction model,24 hours as a stable time point to observe the effect of microcirculation on prognosis,may be conducive to clinicians better grasp the timeliness of treatment.The ROC curve was used to evaluate the effect ofΔPPVs on the early prognosis of septic shock patients.The optimal cut-off point was 4.8%(AUC=0.866 95%Cl=0.750-0.982P=0.000),sensitivity was 0.806,and specificity was 0.812.A total of 52 patients with septic shock were collected and divided into 32 patients in the improved group(ΔPPVs≥4.8%)and 20 patients in the non-improved group(ΔPPVs<4.8%)according to the cut-off point.Through chi-square test evaluation of three methods for recovery period of microcirculation,respectively,33.3%,75.0%and 77.8%,the difference was statistically significant(X~2=9.281,P=0.010).A pairwise comparison using Z-test showed that balanced crystal solution+albumin was statistically different from balanced crystal solution alone and balanced crystal solution+plasma was statistically different from balanced crystal solution alone,but there was no statistical difference between balanced crystal solution+albumin and balanced crystal solution+plasma.Multivariate Logistic regression equation analysis was performed including mean arterial pressure,whether or not high dose vasoactive drugs,SOFA,APACHEⅡ,and resuscitation mode.The results showed that compared with low dose vasoactive drugs,high dose vasoactive drugs may be an obstacle to the improvement of microcirculation(OR=0.021 95%CI=0.001-0.678 P=0.029;maintaining high mean arterial pressure may be beneficial to the improvement of microcirculation(OR=1.310 95%CI=1.047-1.638 P=0.018;higher APACHE II may be a hindrance to the improvement of microcirculation(OR=0.510 95%CI=0.298-0.872P=0.014);There was no statistical difference between different methods of fluid resuscitation.Conclusions1.The integration of perfusion boundary zone and rapid sequential organ failure score has the potential to assist clinicians in early identification and intervention of sepsis.Additionally,it may aid in the selection of specific inflammatory and glycocalyx damage markers with diagnostic value,which can serve as a reference for future research and application.2.The sublingual microcirculation index was notably altered in sepsis patients and correlated with impaired organ function.Its manifestation could occur prior to macrocirculation monitoring indicators.Enhancing microcirculation indicators early on may improve patient prognosis.Continuously monitoring microcirculation changes may aid in predicting patient prognosis and guiding individualized clinical treatment.3.Fluid resuscitation is a crucial component in the treatment of septic shock,and its impact on microcirculation needs to be carefully considered.The effects of colloids,such as albumin and plasma,on microcirculation in patients with septic shock during early fluid resuscitation remain uncertain.Further investigations are needed to explore the"reactivity"of patients’microcirculation to different fluid resuscitation protocols.Meanwhile,factors that affect microcirculation,such as APACHE II score,mean arterial pressure,and the use of high-dose vasoactive drugs,should be screened to establish a foundation for subsequent studies. |