Dynamic Observation Of Sublingual Microcirculation In Patients With Septic Shock And Disseminated Intravascular Coagulation

Objective:Sepsis is caused by infection and accompanied by acute organ dysfunction,which has the characteristics of high morbidity and high mortality worldwide.Septic shock is a special type of sepsis,with a mortality rate of more than 40%.When septic shock occurs,under the influence of inflammatory mediators,the microcirculation vascular endothelium is damaged,vascular permeability is increased,and capillary leakage leads to tissue edema.At the same time,the body’s immune response is activated,a large number of inflammatory factors are released,causing neutrophil endothelial cell adhesion,activating complement and coagulation cascade,leading to a large number of microthrombi,and in severe cases,disseminated intravascular coagulation（DIC）,followed by hyperfibrinolysis.As poor tissue circulation is the key factor leading to infected organ failure,DIC and shock are the two key complications that affect the prognosis of patients.Based on the pathophysiological characteristics of DIC,which is the formation of widespread diffuse microthrombus,sublingual microcirculation imaging was used in this study for the first time to observe the changes of sublingual microcirculation before and after the occurrence of DIC in patients with shock,and to explore the relationship between early sublingual microcirculation and systemic circulation,oxygen metabolism and disease severity in patients with septic shock.Methods:（1）According to the definition of sepsis 3.0 and the inclusion and exclusion criteria,the clinical data of patients with sepsis admitted to the Department of Critical Care Medicine of the First Hospital of China Medical University from February 1,2022to January 30,2023 were collected,and 45 patients were finally enrolled.All subjects were tested for five coagulation tests and blood routine tests at admission and daily.Patients were divided into two groups according to the International ISTH score.ISTH score<5 within 48 hours was defined as Shock group.Shock+DIC group was defined as ISTH score≥5 within 48 hours.（2）All subjects were collected by Microsee V100 sublingual microcirculation imaging system at six time points（T0,T3,T6,T12,T24,and T48）at 0h,3h,6h,12h,24h,and48h after admission to department of Critical Care Medicine.Microsee V100 analysis software was used to carry out a analysis on the image,and calculate the total vessel density（TVD）,perfused vessel density（PVD）,proportion of perfused vessels（PPV）,microvascular flow index（MFI）,heterogeneity index,HI),De Backer score（DB）and total vascular density of small vessels（TVDs）,perfused vascular density of small vessels（PVDs）,proportion of perfused small vessels（PPVs）,De Backer of small vessels（DBs）.（3）The daily sequential organ failure assessment（SOFA）score was evaluated.Macrocirculation and perfusion parameters were collected for all patients at each time point,including:arterio-venous blood gases analysis were collected at the same time points as the collection of sublingual microcirculation,and the levels of lactic acid（Lac）and systemic central venous oxygen saturation（Scv O₂）were measured.Basic vital signs and clinical supportive treatment information including dosage,heart rate（HR）and mean artery pressure（MAP）were recorded at the above time points.（4）Clinical outcomes were evaluated including length of department of Critical Care Medicine stay,duration of mechanical ventilation,cumulative norepinephrine dose within 48 hours,renal replacement therapy,and 28-day mortality.Results:（1）Compared with the Shock group,the parameters of microcirculation density（TVD,TVDs,PVD,PVDs,DB and DBs）and blood flow-related parameters（PPV,PPVs and MFI）in the Shock+DIC group showed a downward trend within 48 hours of continuous dynamic observation.The HI index of vascular heterogeneity showed an overall upward trend,indicating that the level of sublingual microcirculation in Shock patients with DIC gradually deteriorated over time.However,there was no significant change in all the parameters in the Shock group within 48 hours of continuous observation.（2）Compared with the parameters of sublingual microcirculation at the time of diagnosis of DIC,the levels of TVD,TVDs,PVD,PVDs,DB,DBs and blood flow of sublingual microcirculation density at T0 in Shock+DIC group（pre-DIC）were significantly decreased（P<0.05）.There was a significant difference in HI between the two time points before and after ISTH score≥5（P<0.05）.The results indicate that the sublingual microcirculation in shock patients deteriorates further after DIC.（3）In terms of systemic circulation and oxygen metabolism of Shock patients,the heart rate of Shock+DIC group was higher than that of shock group at T0,T3,T6,T12 and T24（P<0.05）.There was no significant difference in MAP and CVP levels between the two groups at each monitoring time point（P>0.05）.The Lac level of Shock+DIC group was higher than that of Shock group at each time point,and the differences were statistically significant at T3,T6 and T12（P<0.05）.In the correlation analysis between the indexes of sublingual microcirculation and the indexes of macrocirculation and oxygen metabolism,the blood lactic acid at 6 hours after shock（T6）was negatively correlated with the indexes of sublingual microcirculation（P<0.05）,and no significant correlation was found at other time points.（4）In the correlation analysis between microcirculation and disease severity,TVD was negatively correlated with Day-2 SOFA score,Day-1 ISTH score and Day-2 ISTH score（P<0.05）.T0 PPV was negatively correlated with Day-1 SOFA score,Day-2 SOFA score and Day-2 ISTH score（P<0.05）.T0 PVD was negatively correlated with Day-1SOFA score,Day-2 SOFA score,Day-1 ISTH score,and Day-2 ISTH score（P<0.05）.（5）In terms of prognostic assessment,the cumulative dose of norepinephrine,proportion of renal replacement therapy,duration of mechanical ventilation,and Day-2platelet-removed SOFA score（the score of the removal of SOFA about coagulation function,namely the increase of platelet items）were statistically significant between the two groups during the observation period（P<0.05）.There were no differences in Department of Critical Care Medicine stay,length of stay and 28-day mortality（P>0.05）.However,the above indexes in Shock+DIC group were higher than those in Shock group.（6）In this study,PLT,PT,and TVD were utilized as test variables while the occurrence of DIC was used as the state variable.Binary logistic regression analysis was employed to establish a diagnostic model for septic shock complicated with DIC,and the area under the ROC curve was calculated.The AUC,sensitivity,and specificity of the area under the curve in diagnosing septic shock with DIC using TVD were 0.838,85.00%,and 88.00%,respectively.In this study,PLT,PT,and TVD were utilized as test variables while the occurrence of DIC was considered as the state variable.A diagnostic model for septic shock complicated with DIC was constructed using binary logistic regression analysis,which combined the aforementioned variables.The model’s effectiveness was evaluated by testing the area under the ROC curve.In the diagnosis of septic shock with DIC,the area under the curve for TVD was 0.838 with a sensitivity of 85.00%and a specificity of88.00%.Similarly,PLT had an AUC of 0.859 with a sensitivity of 80.00%and a specificity of 92.00%.The AUC,sensitivity,and specificity of PT were 0.784,80.00%,and 80.00%,respectively.The combination of TVD,PLT and PT has a high value in predicting septic shock with DIC,and has high sensitivity and specificity,which is superior to using a single detection method alone.Conclusion:In septic shock patients with DIC,the sublingual microcirculation will be significantly impaired,and it will deteriorate dynamically with time.The indicators of sublingual microcirculation at the early stage of septic shock may be related to the development of DIC and poor clinical prognosis.The diagnostic value of TVD combined with conventional coagulation indexes in septic shock complicated with DIC is higher than that of PLT and PT alone.Dynamic monitoring of microcirculation at the early stage of septic shock can screen out high-risk patients with DIC,which is more conducive to clinical screening of the target population of DIC anticoagulation therapy.