OBJECTIVE: To evaluate the risks and benefits of different resuscitation fluids in patients with early sepsis and septic shock by observing and comparing clinical indicators, clinical outcomes, and the concentration changes of glycocalyx biomarkers, and to determine how to appropriately select suitable resuscitation fluids for sepsis patients to aid fluid therapy. METHODS: A single center, prospective, randomized controlled trial was conducted. Patients with early sepsis and septic shock who have required fluid resuscitation after capacity status assessment admitted to the department of critical care medicine of Fourth Hospital of Hebei Medical University from April to October 2023 were enrolled. Patients were randomly assigned to either the experimental group (balanced crystalloid solution+albumin) or the control group (balanced crystalloid solution) by a random number table method. Clinical data of both groups of patients before and after resuscitation at 3, 8, and 24 hours were monitored, and blood samples were collected, enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of plasma glycocalyx biomarker syndecan-1. The 28-day and 90-day survival rates and complications were also assessed. RESULTS: A total of 66 patients were enrolled, including 44 in the experimental group and 22 in the control group. The baseline data of two groups were balanced and comparable. There was no statistically significant difference in the plasma concentration of syndecan-1 between the experimental group and the control group before and after resuscitation, and both showed a trend of first increasing and then decreasing. However, the plasma syndecan-1 level in the control group at 8 hours and 24 hours after resuscitation were significantly higher than the baseline level before resuscitation [ng/L: 19.02 (14.41, 27.80), 18.95 (12.40, 22.50) vs. 14.67 (11.57, 21.14), both P < 0.05], while there was no statistically significant difference at any time point within the experimental group. The correlation analysis between plasma syndecan-1 level and lactic acid, albumin, and sequential organ failure assessment (SOFA) in all patients showed that a positive correlation between syndecan-1 level and SOFA score before resuscitation (r = 0.247, P = 0.046), and a negative correlation between syndecan-1 level and albumin level at 24 hours after resuscitation (r = -0.308, P = 0.012). There were no statistically significant differences in 28-day and 90-day mortality, length of hospital stay, length of intensive care unit (ICU) stay, duration of mechanical ventilation, blood purification time, number of organ injuries, and complications between the two groups. However, the baseline albumin level in the experimental group was significantly lower than that in the control group (g/L: 28.7±4.5 vs. 31.6±4.2, P < 0.05). Analysis of clinical treatment data showed that compared with the control group, the experimental group had lower absolute lactate level at 8 hours and 24 hours after resuscitation [mmol/L: 8 hours was 1.30 (1.00, 1.88) vs. 1.60 (1.30, 3.05), 24 hours was 1.15 (0.80, 1.78) vs. 1.55 (1.08, 2.05), both P < 0.05], and higher lactate clearance rate [8 hours was 45% (27%, 56%) vs. 20% (-4%, 46%), 24 hours was 55% (34%, 70%) vs. 34% (-14%, 59%), both P < 0.05]. However, there were no statistically significant differences in the amount of fluid resuscitation, use of vasoactive drugs, and oxygenation index between the two groups during the resuscitation process. Multivariate Logistic regression analysis showed that body mass index (BMI) was independently correlated with 90-day mortality [odds ratio (OR) = 1.991, 95% confidence interval (95%CI) was 1.023-3.387, P = 0.043]. CONCLUSIONS There are no significant difference in plasma syndecan-1 level during fluid resuscitation of early sepsis and septic shock patients using balanced crystalloid fluid and balanced crystalloid fluid combined with albumin resuscitation, and there are no statistically significant differences in the impact on 28-day and 90-day prognosis, length of hospital stay, complications, and other aspects of the patients. However, compared to balanced crystalloid fluid, the combination of balanced crystalloid fluid and albumin for fluid resuscitation in sepsis patients has lower lactate level and better lactate clearance effect, but further validation is still needed through large-scale randomized controlled trials.
Humans ; Clinical Relevance ; Crystalloid Solutions/administration & dosage* ; Fluid Therapy/methods* ; Glycocalyx/metabolism* ; Isotonic Solutions/administration & dosage* ; Prospective Studies ; Resuscitation/methods* ; Sepsis/therapy* ; Shock, Septic/therapy* ; Syndecan-1/blood*

OBJECTIVE: To explore the protective effect of glycosaminoglycans (GAG) on vascular endothelium in patients with sepsis. METHODS: A prospective study was conducted on adult patients with sepsis admitted to the intensive care unit (ICU) of Hangzhou Normal University Affiliated Hospital from December 2022 to December 2023. Patients were randomly divided into conventional treatment group and GAG intervention group. Both groups were treated according to the 2021 Surviving Sepsis Campaign Guidelines. The GAG intervention group was additionally treated with GAG (2 mL of sulodexide intramuscular injection once daily for 7 days) on the basis of conventional treatment. Venous blood was collected from patients at 0, 6, 24, 48, 72 hours and 7 days after enrollment to detect serum vascular endothelial glycocalyx [heparan sulfate (HS) and syndecan-1 (SDC-1)], inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], and coagulation markers [prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin-III (AT-III), fibrinogen (Fib), D-Dimer], and to perform acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and International Society on Thrombosis and Haemostasis (ISTH) scores. The prognosis of patients (length of hospital stay, ICU and 28-day mortality) was observed. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of HS in predicting the prognosis of sepsis patients, and the correlation between endothelial glycocalyx degradation products and various clinical indicators was analyzed. RESULTS: A total of 50 adult patients with sepsis meeting the inclusion criteria were enrolled, with 25 in the conventional treatment group and 25 in the GAG intervention group. In terms of degradation products of endothelial glycocalyx, compared to baseline, both groups showed an increasing trend in HS and SDC-1 levels post-treatment. However, the GAG intervention group exhibited significantly lower HS levels at 72 hours and 7 days, as well as lower SDC-1 levels at 6, 24, 48, 72 hours and 7 days compared to the conventional group. Among the surviving patients, the HS levels at 72 hours and SDC-1 levels at 6 hours of treatment in the GAG intervention group were significantly reduced compared to the conventional treatment group. In terms of severity score, compared with before treatment, the GAG intervention group showed a significant decrease in APACHE II, SOFA, and ISTH scores after 7 days of treatment. The SOFA scores of the GAG intervention group after 48 hours and 7 days of treatment were significantly lower than those of the conventional treatment group. In terms of inflammatory indicators, compared with before treatment, the GAG intervention group showed a significant decrease in IL-6 levels after 48 hours of treatment. With the prolongation of treatment time, the CRP levels of both groups of patients showed a significant downward trend, and at 7 days of treatment, the CRP level in the GAG intervention group was significantly lower than that in the conventional treatment group. In terms of coagulation function, with prolonged treatment time, PT and APTT of both groups of patients showed an increasing trend, while Fib showed a decreasing trend. The GAG intervention group showed a significant prolongation of PT after 72 hours of treatment compared to the conventional treatment group. In terms of prognosis, there were no statistically significant differences in ICU and 28-day mortality rates between the two groups. The GAG intervention group had significantly shorter hospital stays than the conventional treatment group. ROC curve analysis showed that HS, CRP, APTT, IL-6, APACHE II, SOFA, and ISTH scores were predictive factors for the prognosis of sepsis patients (all P < 0.05). Compared to a single indicator, the combined detection of multiple indicators has a higher value in predicting the prognosis of sepsis patients [area under the curve (AUC) = 0.911, 95% confidence interval (95%CI) was 0.817-1.000], with a sensitivity of 76.9% and a specificity of 91.9%. Correlation analysis showed that HS was significantly negatively correlated with Fib, PT, TNF-α, IL-6, and PCT (r values were -0.338, -0.396, -0.288, -0.319, and -0.340, all P < 0.05), while HS was significantly positively correlated with D-Dimer and CRP (r values were 0.347 and 0.354, both P < 0.05); SDC-1 was significantly negatively correlated with Fib, PT, APTT, TNF-α, IL-6, and ISTH scores (r values were -0.314, -0.294, -0.408, -0.353, -0.289, -0.287, all P < 0.05). CONCLUSIONS Early glycocalyx degradation can occur in sepsis patients. GAG have a protective effect on,the vascular endothelium, reducing the severity of sepsis and providing organ protection. HS, CRP, APTT, IL-6, APACHE II score, SOFA score, and ISTH score are independent predictive factors for the prognosis of sepsis patients. The combination of HS and the above indicators can significantly improve the accuracy of prediction.
Humans ; Sepsis/blood* ; Glycocalyx/drug effects* ; Glycosaminoglycans/pharmacology* ; Prospective Studies ; Endothelium, Vascular/metabolism* ; Syndecan-1/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; Interleukin-6/blood* ; Heparitin Sulfate/blood* ; Middle Aged ; Adult ; Tumor Necrosis Factor-alpha/blood* ; Procalcitonin/blood*

OBJECTIVE: The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of the eGC in various pathologic and physiologic conditions, by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance. We also explored different pharmacologic agents used to protect and rebuild the eGC. DATA SOURCES: An in-depth search was performed in the PubMed database, focusing on research published after 2003 with keywords including eGC, permeability, glycocalyx and injuries, and glycocalyx protection. STUDY SELECTION: Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC. RESULTS: The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia, and high Na as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. CONCLUSIONS Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.
Animals ; Databases, Factual ; Endothelium, Vascular ; metabolism ; pathology ; Glycocalyx ; metabolism ; pathology ; Humans ; Shear Strength

OBJECTIVE: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. METHODS: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. RESULTS: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. CONCLUSIONS Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
Acute Disease ; Animals ; Dexamethasone/pharmacology* ; Disease Models, Animal ; Edema/metabolism* ; Endothelium, Vascular/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Glycocalyx/drug effects* ; Kidney/drug effects* ; Male ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Pancreatitis/drug therapy* ; Perfusion ; Protective Agents/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*