Mass balance of albumin in sepsis

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Septic shock is a leading cause of hospital mortality. Manifest circulatory instability characterizes septic shock, and intravenous infusion of fluids is a cornerstone in the treatment, to maintain blood pressure and blood flow to vital organs. However, the fluid will to some part leak into the interstitial space causing edema, and the size of this weight gain is correlated to mortality and morbidity. Plasma albumin (P-alb) is a negative phase reactant. The effect of albumin is reported to be no more harmful than that of normal saline, but the volume sparing effect of albumin is small in ICU patients. An increased rate of leakage of albumin from the vascular system in septic patients has been demonstrated, but the return of proteins and fluid by the lymphatic system is impossible to measure directly. However, the combined effect of leakage and return can be assessed by albumin mass balance. Thus, the relationship between the negative phase reactant plasma albumin and the amount of albumin accumulating outside the blood vessels can be estimated and increase our knowledge of our present fluid treatment effects. We have previously demonstrated albumin leakage from the blood stream in major abdominal surgery by albumin mass balance describing the relationship between albumin within and outside the vascular system perioperatively. We want to apply the same technique to septic ICU patients. In this observational study we investigate patients with severe sepsis/septic shock. We will collect blood samples during the first 24 hrs in ICU and quantify cumulative albumin shift, i.e. the amount of albumin accumulating supposedly in the extracellular space. We will also characterize markers of endothelial injury (components of the glycocalyx), markers of inflammations (interleukins) and indices of volume status (fluid balance, weight gain, rate of infusions). Finally all these indices will be correlated to albumin kinetic parameters to generate hypothesis for future studies. The overall aim of our research program is to define the role of albumin in modern fluid therapy. This study is an important step to understand the effects of our present fluid strategy on the vasculature, and to generate new hypotheses on the mechanisms. Future studies will depend on these results.

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