Lisa Smart

Synthetic colloid fluids are frequently used for blood volume expansion in critically ill patients. Starch-based synthetic colloid fluids have been associated with increased risk of acute kidney injury. There is some evidence that gelatine-based colloid fluids may also pose a similar risk. This randomised open-label controlled pilot trial will assess the effects of 4% succinylated gelatine fluid on urinary biomarkers of acute kidney injury in Intensive Care Unit (ICU) patients. This study will also assess clinical outcomes, as secondary endpoints, including change in AKI stage, need for renal replacement therapy (RRT), ICU length of stay and mortality.

Background: Endothelial glycocalyx damage (EGD) biomarkers are associated with poor outcomes in ICU patients with sepsis but there is little information on behaviour of these biomarkers in Emergency Department (ED) patients with infection.

Objectives: 1) To explore three biomarkers of EGD in ED patients with infection over the first 24 hours, 2) to compare these results to a trauma group, and 3) to explore associations with illness severity, comorbidities and clinical outcomes in patients with infection.

Methods: Banked serum samples were used from patients with simple infection (n = 22), sepsis (43), septic shock (45) and trauma (30) collected at: enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12–24 hours (T24) later. Healthy controls (n = 29) were included for T0 comparisons. Biomarkers syndecan-1 (SYN1), syndecan-4 (SYN4) and hyaluronan (HA) were measured via ELISA. Results were obtained using regression methods including random effects linear, logistic and truncated negative binomial methods. Significance was set at P < 0.05.

Results: SYN1 concentration at T0 was significantly higher in all groups compared to control (median 494pg/ml, [Q1-Q3 382–709]). Septic shock (3064pg/ml, [1645–7116]) and sepsis (2542, [1096–5263]) groups had significantly higher concentrations than simple infection (1207, [695–1647]) and trauma (1404, [1055–2265]). SYN1 increased between T0 and T24 in the simple infection and septic shock groups, which was significantly different to trauma.

SYN4 was not different among groups at T0. A decrease in SYN4 in the simple infection group at T3 was the only between-group difference.

HA concentration was significantly higher in the septic shock group at T0 (128 ng/ml, [62–425]) than simple infection (32, [13–89]), sepsis (62, [22–135]), trauma (45, [15–82]) and healthy control groups (41, [24–60]). HA increased between T0 and T3 in infection groups, whereas HA decreased between T0 and T3 in trauma.

Patients with liver disease or alcohol abuse had significantly higher SYN1 and HA over time, compared to others. Patients with vascular disease failed to show a peak in HA concentration at T3, compared to others. Higher SYN1 and HA at T0 significantly increased the odds of ICU admission and higher sequential organ failure assessment score.

Conclusions: ED patients with sepsis and septic shock had higher levels of EGD biomarkers compared to those with simple infection or trauma. Differing patterns of EGD occurred over the first 24 hours of hospitalisation for infection, compared to trauma. Increased SYN1 and HA was also related to key comorbidities, ICU admission and organ failure

Background: Ongoing work by our group found differences in endothelial glycocalyx damage (EGD) biomarker expression over time in Emergency Department (ED) patients with infection and trauma. This may be explained by varying levels of inflammation or endothelial activation. Objectives: To explore associations of three EGD biomarkers with inflammatory and endothelial activation biomarkers in patients with infection or trauma. Methods: Banked serum samples were used from patients with simple infection (n = 22), sepsis (43), septic shock (45) and trauma (30) collected at: enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12–24 hours (T24). EGD biomarkers included syndecan-1 (SYN1), syndecan-4 (SYN4), and hyaluronan (HA). Inflammatory biomarkers included interleukin-6 (IL6), interleukin-10 (IL10), neutrophil gelatinase-associated lipocalin (NGAL), resistin (RTN) and C-reactive protein (CRP). Endothelial activation biomarkers included intercellular adhesion molecule-1 (ICAM) and vascular cell adhesion molecule-1 (VCAM). Laboratory methods included ELISA and cytometric bead array. Random effects linear regression was used to explore associations over time. Only significant results (P < 0.05) are presented. Results: SYN1 was positively associated with IL6 (T24 in sepsis, T3 and T24 in trauma). SYN4 was positively associated with IL6 in septic shock (T0, T1 and T3). In contrast, SYN4 was negatively associated with IL6 in simple infection at T24. HA was positively associated with IL6 (T3 in septic shock, T24 in trauma). SYN1 and SYN4 were positively associated with IL10, with no differences between groups or over time. SYN1 and SYN4 were positively associated with RTN and NGAL at multiple time points in the infection groups, however only associations with SYN1 showed change over time. HA was positively associated with RTN at multiple time points (T0 in sepsis, T1, T3 and T24 in septic shock, T3 and T24 in trauma), as well as NGAL (T0, T1 and T24 in sepsis, T24 in septic shock and trauma). SYN4 was positively associated with ICAM at T0, T1 and T3 in trauma, whereas HA had an overall negative association with ICAM and VCAM in trauma. Conclusions: EGD biomarkers showed positive associations with inflammation in the infection groups, varying with biomarker, time point and illness severity. Associations with inflammation in trauma were later in hospitalisation. Only the trauma group showed an association between EGD and endothelial activation. Further investigation into the mechanism of EGD biomarker release in critically ill patients is required.