The Effect Of Glycocalyx Degradation On Tissue Perfusion In Septic Shock

Objectives:(1) To determine the effect of microcirculation dysfunction on tissue perfusion and prognosis in septic shock patients.(2) To investigate whether glycocalyx degradation can change critical closing pressure (Pcc), and its effect on microcirculation dynamics in animal models.(3) To investigate the effect of microcirculation blood flow and distribution on oxygen delivery, to distinguish cytopathic hypoxia from microcirculation dysfunction by the relationship of oxygen delivery and lactate in animal models.Methods:(1) To retrospectively analysis septic shock patients admitted in ICU, Peking Union Medical College Hospital from July 2013 to March 2015. All patients received early goal directed therapy and achieved central venous pressure (CVP)≥8 mmHg, mean arterial pressure (MAP)≥65 mmHg, cardiac index (CI) 2.4～4.0 L/(min·m2). According to the venous-arterial carbon dioxide partial pressure/arterio-venous oxygen content difference (Pv-aCO2/Ca-vO2) and Pv-aCO2, patients were divided into control group, hypoperfusion group, normal perfusion group. Their hemodynamic parameters and 28-day mortality were recorded. SPSS 19.0 is used for statistical analysis.(2) Healthy adult rabbits were divided into four groups:C group (0.9% sodium chloride, iv.), HA group (hyaluronidase, iv.), E group (lipopolysaccharide, iv.), E+H group (lipopolysaccharide+hydrocortisone, iv.). At baseline and 30,60,90,120,180 min after injection, arterial blood gas analysis were performed, Pcc, mean systemic filling pressure (Pmsf), red blood cell-endothelial cell gap (EEC gap) and functional capillary density (FCD) were measured. SPSS 19.0 is used for statistical analysis.(3) In addition to part 2, transcutaneous oxygen tension (PtcO2) and transcutaneous carbon dioxide tension (PtcCO2) were measured at each time point. SPSS 19.0 is used for statistical analysis.Results:(1) The APACHE II, temperature, heart rate, CVP, MAP, CI, hemoglobin and arterial oxygen saturation in three groups didn’t have significant difference. The lactate clearance rates at 6 h and 24 h in hypoperfusion group were significantly lower than in the control group. Pv-aCO2 was negatively correlated with lactate. The mortality in hypoperfusion group and normal perfusion group were significantly higher than in the control group. APACHE II, lactate, lactate clearance rate at 24 h and Pv-aCO2/Ca-vO2 were risk factors of mortality.(2) The EEC gap, Pcc and FCD% in HA group were significantly lower than in C group at 30～90 min, in E group were significantly lower than in C group from 30 min, in E+H group were significantly lower than in C group from 90 min. MAP-Pcc in HA group slightly increased at 30～90 min, in E group was significantly lower than in C group from 90 min, in E+H group was significantly lower than in C group from 120 min. Pcc was positively correlated with EEC gap and MAP, EEC gap was positively correlated with FCD%.(3) PtcO2 in HA group slightly decreased at 30～60 min, in E group was significantly lower than in C group from 60 min, in E+H group was significantly lower than in C group from 90 min. Lactate in HA group slightly increased at 30～60 min, in E group was significantly higher than in C group from 30 min, in E+H group was significantly higher than in C group from 90 min. EEC gap and FCD% was positively correlated with PtcO2, Ptc-aCO2 was negatively correlated with PtcO2, lactate was negatively correlated with PtcO2. Linear regression shows FCD%=1.56×PtcO2+0.64 ×Ptc-aCO2-0.17; lactate in HA group=-0.087×PtcO2+6.61, lactate in E group=-0.145×PtcO2+10.74.Conclusions:(1) Although EGDT targets were achieved, tissue hypoxia existed and became the main reason for mortality in septic shock. Tissue hypoxia included microcirculation dysfunction and cytopathic hypoxia, Pv-aCO2/Ca-vO2and Pv-aCO2were helpful to distinguish them. The improvement of tissue oxygenation was slower, lactate clearance rate was lower in microcirculation dysfunction. Oxygen consumption was decreased in microcirculation dysfunction and cytopathic hypoxia. Pv-aCO2/Ca-vO2is a risk factor for mortality.(2) Glycocalyx degradation decreased Pcc and FCD, this is one of the mechanisms of microcirculation maldistribution in septic shock. The decrease of Pcc can increase blood flow in microcirculation, promote hypovolemia in early phase of septic shock. Hydrocortisone can protect glycocalyx to prevent the decrease of Pcc and FCD, maintain the stability of microcirculation. The decrease of Pcc is early than the decrease of MAP in septic shock. Monitoring pressures in microcirculation were help to early identification of septic shock. Pcc did not have a causal relationship with arterial or venous pressure.(3) Glycocalyx degradation had two effects on tissue oxygen delivery:① decrease FCD and induce tissue hypoxia;② increase blood flow in microcirculation and increase oxygen delivery. The combined effect is decrease of oxygen delivery. In septic shock, the decrease of FCD, combined with the decrease of microcirculation blood flow, can lead to tissue hypoxia. Microcirculation blood distribution parameter can be calculated from oxygen and flow parameters, and can be used to determine blood maldistribution. The reason of lactate elevation in septic shock includes microcirculation dysfunction and cytopathic hypoxia, which could be distinguished by the relationship of tissue oxygen and lactate level.