Albumin mass balance and markers of endothelial injury in pancreatic surgery

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Background Intravenous fluids are regularly used during major abdominal surgery. A vivid debate on infusion rates, guidance, and choice of fluids is ongoing. Colloids are larger molecules that stay longer (hours) in plasma, but long term effects (weeks or more) are poorly investigated. After the recent recommendation against the use of the synthetic colloid hydroxyethyl starch by the European Medical Agency for safety reasons, albumin containing solutions remain the most used colloid in Sweden and at Karolinska University Hospital. However, evidence of any long term beneficial effects of albumin is missing. Albumin is the main constituent of plasma proteins, contributing to the colloid osmotic pressure in the capillaries. Normally, it leaves the blood stream through the capillary walls at a rate of 4-5% of the intravascular pool per hour, and returns to plasma by the lymph at the same rate. Being an endogenous substance, it carries low risk of adverse effects, but the dosing is controversial, and costs high. We have previously demonstrated a cumulative perioperative albumin shift of 24 +/- 17 g at the end of major abdominal surgery not explained by bleeding when starch was used as intravenous fluid. We believe that this amount of albumin is displaced to the interstitium, possibly contributing to edema. If capillary leakage is induced by hypervolemia, inflammation or other mechanisms is unclear. Study purpose In this observational study we are looking at two patient groups scheduled for pancreaticoduodenectomy because of malignant or benign disease, respectively. The primary purpose is to find if albumin is lost from the blood even when only crystalloids are used during surgery, our present routine. The malignant patients are likely to lose albumin quicker through the capillary walls because they suffer from chronic inflammation and also have a slower lymphatic return because surgery in that case comprises lymphadenectomies and a more extended dissection. We also want to investigate markers of injury to the capillary walls, markers of inflammation, and indices of volume status to generate new hypotheses. The primary hypothesis is that albumin is lost in both patient groups, but more so in the malignant group, at the end of surgery. The overall aim of our research program is to define the role of albumin in modern fluid therapy. This observational study is an important step in understanding effects of our present fluid routine in major abdominal surgery, to find when and to what degree albumin is lost from the blood stream, and to generate hypotheses on mechanisms. Future interventional studies will depend heavily on these results.

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