Sepsis is a major cause of mortality worldwide, with intravenous crystalloid infusion being the first-line treatment to maintain organ perfusion. However, fluid overload is associated with poor outcomes, and restrictive fluid therapy has not shown benefits. Albumin, due to its molecular properties, may help retain fluid intravascularly, but its volume-sparing effect in sepsis remains debated, leading to weak guideline recommendations despite its widespread use.
Increased transcapillary escape rate (TER) of albumin has been observed in septic patients, but this does not account for lymphatic return. Recent studies in surgical patients suggest albumin accumulation in the interstitium, measured through net albumin leakage (NAL). Capillary patency, influenced by factors like transmural pressure, plasma expansion, and endothelial glycocalyx damage, plays a role in albumin leakage. Glycocalyx shedding, linked to inflammation and fluid administration, has been observed in sepsis but lacks a clear correlation with mortality.
A recent study aimed to assess NAL in septic patients early in their ICU stay and explore its correlation with glycocalyx shedding, inflammation, and fluid overload. Researchers hypothesised that NAL would be positive and associated with these factors.
The study included ten patients within 12 hours of ICU admission for suspected sepsis at Karolinska University Hospital Huddinge. Albumin, haematocrit, and haemoglobin levels were measured at multiple time points over 24 hours. NAL was estimated using mass balance calculations by comparing proportional changes in albumin and haemoglobin concentrations, adjusted for infusions and losses. A disproportionately greater decrease or smaller increase in albumin compared to haemoglobin indicated net albumin leakage from circulation to the interstitium, accounting for lymphatic return.
Patients exhibited a lower NAL (8 ± 10 g) compared to surgical patients (24 ± 17 g), possibly due to pre-ICU albumin leakage or a steady state between leakage and lymphatic return. NAL initially correlated with pro-inflammatory cytokines IL-6 and IL-8 but not with glycocalyx shedding products or fluid balance. Albumin infusions appeared to increase NAL, and a higher serum albumin level at ICU admission showed a non-significant correlation with increased NAL.
The study found no direct link between NAL and TER, as stable disease states like cancer can balance high TER with lymphatic return. Patients had a net positive fluid balance and weight gain, suggesting albumin might mobilise from the interstitium faster than fluid. Elevated shedding products (syndecan-1 and hyaluronan) were observed but did not correlate with NAL.
A post hoc analysis suggested that high albumin levels might indicate an early disease stage with ongoing leakage, whereas low levels could reflect a later stage with higher interstitial albumin concentration aiding return. Regression analysis confirmed that albumin supplementation was associated with increased NAL, consistent with expected physiological distribution. Findings are hypothesis-generating and highlight the need for larger studies to explore these mechanisms further.
Overall, this study shows that in 24 hours, patients with suspected sepsis exhibited a NAL of 8 ± 10 g, likely into the interstitium. A weak correlation was observed between NAL and pro-inflammatory cytokines in the first 4 hours, but no correlation was found with fluid balance or glycocalyx shedding products. Albumin infusions appeared to increase NAL.
Source: Critical Care
Image Credit: iStock
