The Importance of Albumin Infusion Rate for Plasma Volume Expansion. AIR. A Phase III Assessor Blinded Parallel Group Randomized Study

Major surgery is one of many triggers of a systemic inflammatory response syndrome (SIRS), which disrupts the normal regulation of transcapillary fluid exchange with tissue oedema and hypovolemia as a consequence. Hypovolemia will amplify the inflammatory reaction by reducing cardiac output and oxygen delivery, which creates a vicious circle. Fluid therapy is therefore a cornerstone in the perioperative treatment patients subjected to major surgery. However, even if fluid therapy is life saving it is also associated with side effects such as further oedema formation, coagulopathy and further endothelial dysfunction.

From a clinical perspective, it is therefore important that the fluid administered to antagonize hypovolemia as far as possible remains intravascularly. Colloids are macromolecules for which the vessel wall has a low permeability and proponents of colloid containing fluids argues that less volume is required for equal plasma volume compared to crystalloids. However, extravasation of colloids is not only a function of the vessel wall permeability but is also dependent on the volume of fluid to that is filtered across the vascular wall, which in turn depends on the trans-capillary hydrostatic pressure. This means that administration of colloids in a way that minimizes the increase in capillary pressure could be important for the plasma volume expanding effect.

In support of this hypothesis is the experimental result that the plasma volume expansion of a colloidal solution can be affected by the rate of administration (Bark et al., 2013). If this finding proves to be valid also in a clinical setting, it will be very important for how colloidal solutions are prescribed in the clinic and may change current clinical practice in which suspected hypovolemia often is treated with a bolus infusion of fluid. This study intend to investigate whether these findings can be reproduced after a so-called Whipple's operation or after major gynaecological cancer surgery.

Study patients will be studied after these procedures because because they are large and standardized operations that trigger an inflammatory condition with capillary leakage and therefore can be considered as a model for major surgical procedures as well as ICU patients with SIRS triggered by for example sepsis.