Introduction
Background
Components and structure
Glycocalyx function in health and disease
Degradation of the endothelial glycocalyx during sepsis
Vascular heterogeneity of the glycocalyx layer
Measures of glycocalyx degradation in sepsis
Direct bedside imaging of glycocalyx degradation during sepsis
Quantification of septic glycocalyx degradation using circulating biomarkers
Syndecan-1
Year | Authors | Design | Patients population | Patient classification | N | Outcome | Brief result | |
---|---|---|---|---|---|---|---|---|
Syndecan-1 | 2008 | Nelson et al. [34] | Obsevational | Intensive care unit | Cont vs Septic shock | 18 vs 18 | septic shock | Septic shock significantly higher median syndecan-1 vs healthy controls (246 [IQR 180-496] vs 26 ng/ml, [23 - 31], p<0.01) |
Septic shock | 18 | Mortality | No significant association of syndecan-1 with mortality | |||||
Septic shock | 18 | Severity | Septic shock significantly higher median syndecan-1 vs healthy controls (246 ng/mL, [180-496] vs 26 ng/ml, [23 - 31], p<0.01) | |||||
2011 | Steppan et al. [35] | Obsevational | (not specifically referred ) | Cont vs Abdominal surgery vs Severe sepsis or septic shock | 18 vs 28 vs 104 | Severe sepsis or septic shock | Septic patients significantly higher mean syndecan-1 than healthy control (160±109 vs 20.5± 5.1 ng/mL, p<0.001) and than surgery patients (50.5±46.9 ng/mL, p=0.001) | |
Severe sepsis or septic shock | 104 | Level of IL-6 | Syndecan-1 significantly correlated with IL-6 (p=0.004) | |||||
2012 | Sallisalmi et al. [36] | Obsevational | Intensive care unit | Cont vs Septic shock | 20 vs 20 | septic shock | Septic shock higher median syndecan-1 vs controls (p<0.0001) | |
Septic shock | 20 | Severity | syndecan-1 corelates with SOFA score (r=0.654, p<0.002) | |||||
Septic shock | 20 | Level of VAP-1 | syndecan-1 correlated with VAP-1 level (r=0.729, p<0.0001) | |||||
2013 | Ostrowski et al. [73] | Obsevational | Intensive care unit | Experimental endotoxemia vs Severe sepsis or septic shock | 9 vs 20 | Presence of Severe sepsis or septic shock | Septic patients had higher syndecan-1 vs experimental endotoxemia patients (172 ± 102 VS 51 ± 12 ng/mL, p <0.05) | |
Severe sepsis or septic shock | 20 | Severity | No significant correlations of syndecan-1 level with SOFA score (r=0.42, p=NS) and SAPS2(r=0.04, p=NS) | |||||
Severe sepsis or septic shock | 20 | Level of biomarkers | Syndecan-1 correalted with noradrenaline (r=0.45, p=0.045), adrenaline(r=0.62, p=0.004), lactate(r=0.77, p<0.001), APTT(r=0.63, p=0.005), INR(r=0.57, p=0.013) | |||||
2014 | Donati et al. [74] | RCT | Intensive care unit | Non-leukodepleted RBC transfusion vs leukodepleted RBC transfusion | 10 vs 10 | Level of syndecan-1 | In non-leukodepleted RBC transfusion group, the median level of syndecan-1 was significantly increased. No significant association between syndecan-1 and leukodepleted RBC transfusion | |
2014 | Johansson et al. [75] | Obsevational | Intensive care unit | Severe sepsis or septic shock | 67 | Treatment with noradrenalin infusion at the time of blood sampling | No significant association between syndecan and noradrenaline infusion. (p=0.902, data not shown) | |
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Level of biomarkers | Significant correlations of syndecan-1 level with noradrenaline (r=0.29, p=0.034), sTM(r=0.35, p=0.01), hcDNA(r=0.29, p=0.038), protein C(r=-0.56, p<0.0001), tPA(r=0.44, p=0.001), sVEGFR1(r=0.56, p<0.0001), Ang-1(r=-0.51, p<0.001), Ang-2(r=- 0.40, p=0.003), TFPI(r=0.44, p=0.001), platelet count(r=-0.45, p=0.001), creatinine(r=0.34, p=0.012), bilirubin(r=0.45, p=0.001) | |||||
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Presence of septic shock | Significant correlation of syndecan-1 level with shock. (r=0.40, p=0.003) | |||||
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Severity | There were significant correlations of syndecan-1 level with SOFA score (r=0.33, p=0.027) and SAPS2 (r=0.33, p=0.015) | |||||
2015 | Straat et al. [67] | Obsevational | Intensive care unit | non-bleeding critically ill patients | 33 | Level of syndecan-1 | The median level of syndecan-1 after fresh frozen plasma transfusion was significantly lower than the level before the transfusion (565 [IQR 127–1176] ng/mL vs 675 [IQR 132–1690] ng/mL, p=0.01) | |
2015 | Ostrowski et al. [76] | Obsevational | Intensive care unit | Severe sepsis or septic shock | 184 | Coagulopathy | There were siginificant associations of syndecan-1 with TEG R-time (β: 0.64 ± 0.25, p=0.013), TEG MA (β: -1.78 ± 0.87, p=0.042) and FF MA (β: -0.84 ± 0.42, p=0.045) | |
2015 | Ostrowski et al. [37] | Obsevational | Department of internal medicine | No infection vs Local infection vs Sepsis vs Severe sepsis vs Septic shock | 50 vs 63 vs 95 vs 100 vs 13 | Presence of severe sepsis or septic shock | Septic shock (61 ng/mL, [IQR 39 - 119], p<0.05), severe sepsis (61 ng/mL, [IQR 35 - 95], p<0.05) had a significantly higher median level of syndecan than sepsis (31 ng/mL, [IQR 22 - 50]) | |
No infection or Local infection or Sepsis or Severe sepsis or Septic shock | 321 | 28 days mortality | There was a significant association of the median syndecan-1 level with comulative survival over 28days. (p=0.029) | |||||
2016 | Anand et al. [77] | Obsevational | Intensive care unit | Cont vs Sepsis vs Severe sepsis vs Septic shock | 50 vs 15 vs 45 vs 90 | Presence of sepsis | Septic shock (653.5 ng/mL, [IQR 338.93 - 1430.23], p<0.001), severe sepsis(342.1 ng/mL, [IQR 130 - 568.1], p<0.001) and sepsis patitents(85.78 ng/mL, [IQR 40.16 - 141.2], p<0.001) had a significantly higher median level of syndecan than healthy control(28.15 ng/mL, [IQR 7.47 - 45.7]) | |
Sepsis or Severe sepsis or Septic shock | 150 | 90 days mortality | Non-survivor had a significantly higher median level of syndecan-1 than survivor (782 ng/mL, [IQR 235.5 - 1514.31 vs 412.3 ng/mL, [IQR 135.25 - 855.34]; p=0.007). AUC of syndecan-1 level for mortality was 0.644 [95%CI 0.54-0.74]. There was a significant association of the cut off level of syndecan-1:625 ng/ml on DAY 1 ICU admission with comulative survival on Kaplan-Meier plot (p=0.003) | |||||
Sepsis or Severe sepsis or Septic shock | 150 | Severity | There were significant correlations between syndecan-1 levels level with SOFA score (r=0.437, p<0.001) and APACHE2 score (r=0.294, p<0.001). | |||||
2016 | Puskarich et al. [38] | Obsevational | Emergency department | Severe sepsis or septic shock | 175 | Intubation | Intubated patients had syndecan-1 similar to non-intubated patients (181 ng/mL [61 - 568] vs 141 ng/mL [46 - 275], p=0.06) | |
Severe sepsis or septic shock | 175 | Mortality | Non-survivor had a significantly higher level of syndecan-1 than survivor ( 223 ng/mL [67 - 464] vs 142 ng/mL [38 - 294], p=0.04) | |||||
Severe sepsis or septic shock | 175 | Development of AKI | Patients with AKI developlment had a significantly higher level of syndecan-1 than those without AKI development (193 ng/mL [IQR, 63 - 441] vs 93 ng/mL [IQR 23 - 187], p<0 .001) | |||||
Heparan sulfate | 2011 | Steppan et al. [35] | Obsevational | not shown | Cont vs Abdominal surgery vs Severe sepsis or septic shock | 18 vs 28 vs 104 | Severe sepsis or septic shock | Septic patients had a significantly higher mean level of heparan sulfate than healthy control (3.23 ± 2.43 μg/ml vs 1.96 ± 1.21 μg/ml, p = 0.03). Septic patients had a significantly lower mean level of heparan sulfate than surgery patients (3.23 ± 2.43 μg/ml vs 7.96 ± 3.26 μg/ml, p <0.001) |
2014 | Nelson et al. [39] | Obsevational | Intensive care unit | Cont vs Septic shock | 24 vs 24 | septic shock | Septic shock patients had a significantly higher mean level of heparan sulfate than control (p<0.001, data not shown) | |
Septic shock | 24 | Severity | There was a significant correlation between heparan sulfate level with SOFA score (r=0.47, p=0.02) | |||||
Septic shock | 24 | Mortality | Non-survivor had a significantly higher mean level of heparan sulfate than survivor (p=0.02, data not shown) | |||||
Septic shock | 24 | Level of biomarkers | There were no significant correlations of heparan sulfate level with the levels of IL-6 (r=0.40, p=0.06), IL-10 (r=0.34, p=0.10), CRP (r=-0.19, p>0.3), and MPO (r=0.21, p>0.3) | |||||
2016 | Schmidt et al. [41] | Obsevational | Intensive care unit | Severe trauma vs Septic shock | 25 vs 30 | Septic shock | Septic shock patients had a significantly highe mean level of heparan sulfate than sever trauma patitents (p<0.05, data not shown) | |
No AKI development vs AKI development in Septic shock | 16 vs 14 | Development of AKI | Patient who developed AKI had a significantly higher mean level of heparan sulfate than those who do not (p<0.05, data not shown) Non adjusted AUC for the development of AKI was 0.7634 (p=0.014). Aadjusted AUC was not significant (data not shown) | |||||
Septic shock | 30 | Mortality | Non-survivor had a significantly higher mean level of heparan sulfate than survivor (p<0.05, data not shown) | |||||
Non adjusted AUC for the mortality was 0.86 (p=0.0009) Adjusted AUC was 0.91 (p=0.0003) | ||||||||
Hyaluronan | 2012 | Yagmur et al. [42] | Obsevational | Intensive care unit | No SIRS vs SIRS vs Sepsis(sepsis, severe sepsis or septic shock) without cirrhosis | 20 vs 33 vs 97 | Sepsis | Septic patients(344 μg/ml [IQR 0 – 2641]) had a significantly higher median level of hyaluronan than No SIRS (115.5 μg/L [IQR 10 – 2457], p=0.014) and SIRS patients (168 μg/L [IQR 0 – 2117], p=0.015) |
Severity | Hyaluronan correalted with SOFA score (r=0.278, p=0.001) | |||||||
Level of biomarkers | Hyaluronan correlated with Procalcitonin(r=0.46, p<0.001), CRP (r=0.34, p<0.001), IL-6 (r=0.34, p=0.004) and IL-10 (r=0.38, p=0.001) | |||||||
2014 | Nelson et al. [39] | Obsevational | Intensive care unit | Cont vs Septic shock | 24 vs 24 | Septic shock | Septic had a significantly higherdisaccharides from hyaluronan than control (p<0.001) | |
Septic shock | 24 | Severity | Hyaluronan correlated with SOFA score (r=0.47, p=0.02) | |||||
Septic shock | 24 | Mortality | Non survivor had a significantly higher disaccharides from hyaluronan than survivor (p=0.006, data not shown) | |||||
2016 | Schmidt et al. [41] | Obsevational | Intensive care unit | Sever trauma vs Septic shock | 25 vs 30 | Septic shock | Septic shock patients had a significantly higher level of hyaluronan than sever trauma patitents (p<0.05, data not shown) | |
No AKI development vs AKI development in Septic shock patients | 16 vs 14 | Development of AKI | Patient who developed AKI had a significantly higher level of hyaluronan than not (p<0.05, data not shown) | |||||
Septic shock | 30 | Mortality | Non adjusted AUC for the development of AKI was 0.75 (p=0.018) | |||||
Adjusted AUC was 0.77 (p=0.01) | ||||||||
Non survivor had a significantly higher level of hyaluronan than survivor (p<0.05, data not shown) | ||||||||
Non adjusted AUC for the mortality was 0.86 (p=0.0009). Adjusted AUC was not significant (data not shown) |