Introduction: The microcirculation plays a central role in sepsis pathophysiology and is critically dependent on endothelial integrity, which is frequently impaired in this setting. Despite fluid resuscitation being a cornerstone of early sepsis management, the optimal fluid type remains debated. Albumin has demonstrated a favourable safety profile in large trials, but consistent improvements in clinical outcomes have not been observed. Our systematic review identified significant heterogeneity in microcirculatory endpoints, fluid type, and bolus volume, highlighting the need for targeted, mechanistic studies. Methods: We conducted a prospective, semi-blinded, randomised controlled trial to evaluate the effects of 20% albumin compared with crystalloid on the microcirculation in fluid-responsive septic patients. A total of 103 adults were enrolled in a tertiary ICU in Ireland. Fluid responsiveness was assessed using pulse pressure variation, and patients were randomised to receive either 20% albumin or crystalloid. Fluid boluses were titrated to clinical effect. Microcirculatory function was assessed at baseline and post-resuscitation using sidestream dark field (SDF) imaging, analysed with AVA 4.3 software. Results: Among the 100 patients analysed, mean age was 58 years (range 18–86), 35% were female, and mean APACHE II score was 28. There were no significant differences in SOFA scores (9.1 vs 9.8, p = 0.32) or fluid volume administered (405.4 mL vs 481.2 mL, p = 0.145) between groups. Regression analysis showed that patients who received albumin had significantly greater improvement in microvascular integrity, density and perfusion one hour after resuscitation (p < 0.005), with more sustained effects in small vessel flow when compared to crystalloid. No significant differences were seen in vasopressor days, ICU length of stay, or mortality. Conclusions: Our systematic review led us to conduct the largest randomised study to date assessing in vivo microcirculatory effects of hyperoncotic albumin in sepsis. These findings support a physiological effect consistent with proposed endothelial mechanisms and suggest a potential role for albumin in microvascular restoration.
Cusack et al. (Sun,) studied this question.