Elke Rudloff,     Glendale, Wisconsin

Rebecca Kirby,     Glendale, Wisconsin

Fluid Dynamics

The body fluids are distributed between three major compartments: intracellular, intravascular, and interstitial. The cellular membrane defines the intracellular space and is freely permeable only to water. Most ions must enter the cell by specific mechanisms such as channels, solvent drag, carriers, or pumps. Intracellular ions help retain water within the cell by osmosis. The intravascular space is contained within a vascular semipermeable “membrane” composed of a single thin glycocalyx surface lining the endothelium. Fluid and nutrient exchange between the blood and the tissues occur primarily at the level of the capillary membrane. Larger molecules such as the plasma proteins (albumin, fibrinogen, and globulins) are too large to freely cross this semipermeable membrane.

The modified Starling-Landis equation defines the forces that control the rate of the flow of fluid between the capillary and interstitium as:

The main components that control intravascular fluid volume include intravascular colloid osmotic pressure (COP) and hydrostatic pressure (HP) (Figure 2-1). Eighty percent of the COP is produced by albumin, which is the most abundant extracellular protein. The pressure generated by albumin is augmented by its negative charge, which attracts cations (e.g., sodium) and water around its core structure. This unique dynamic is termed the Gibbs–Donnan effect. Vascular permeability to ion species, ionic concentration gradients, and electrochemical charges influence the movement of ions such as sodium, potassium, and chloride. Capillary membrane pore size and the filtration coefficient control the ease with which larger molecules such as albumin leave the intravascular space. Pore size varies from tissue to tissue (e.g., continuous capillaries in the brain and fenestrated capillaries in the liver). The filtration coefficient is variable and partly dependent on the amount of albumin in the intravascular space and within the interendothelial cleft.

The dynamics of normal fluid movement across the capillary membrane can change with certain diseases. Fluid moves from the intravascular to the interstitial or third-space compartment under certain conditions (Figure 2-2 and Table 2-1). Plasma COP can increase with water loss (hemoconcentration), remain the same when there is acute hemorrhage, or decrease with protein loss. In addition to capillary dynamics, the composition of intravenously administered fluids determines how these fluids are distributed across fluid compartments.

Basic Colloid Fluid Pharmacology

The two major categories of intravenous fluids are crystalloids (see Chapter 1) and colloids. A crystalloid fluid is a water-based solution with small molecules permeable to the capillary membrane. A colloid fluid is a crystalloid-based solution that contains large molecules that do not easily cross normal capillary membranes. When large volumes are needed for intravascular fluid resuscitation, crystalloids alone may fail to provide effective intravascular volume support without causing interstitial volume overload and edema.

Ultimately the selection of a colloid or a combination of a colloid with a crystalloid for intravenous resuscitation and maintenance is based on the pharmacology of the fluid and the disorder that requires treatment. Each colloid solution is unique, and knowledge of the composition and pharmacology of the fluid is needed to make an appropriate colloid selection for an individual patient’s needs (Table 2-2). Differences in macromolecular structure and weight dictate the colloid osmotic effect, method of excretion, and half-life of the colloid solution. The larger the number of small molecules per unit volume of the colloid, the greater will be the initial colloid osmotic effect and plasma volume expansion. When the number of large molecules per unit volume of colloid is high, the colloid is retained longer within the vascular space.

Solutions that contain naturally produced proteins such as albumin (whole blood, plasma products, and concentrated human and canine albumin solutions) or hemoglobin (hemoglobin-based oxygen carriers [HBOCs]) are referred to as natural colloids. Solutions that contain synthetically derived colloid particles such as hydroxyethyl starches (HESs) (hetastarch and tetrastarch) are referred to as synthetic colloids.

Large-volume fluid resuscitation decreases the concentration of coagulation proteins in the plasma and can cause a dilutional coagulopathy. Synthetic colloids are not a substitute for blood products when albumin, hemoglobin, antithrombin, or coagulation proteins are needed. At the present time, albumin products and HESs are the most readily available and commonly used colloids in the United States. Although HBOCs are not available for clinical use at this time, they are being continuously evaluated in experimental studies and are expected to be reintroduced in the near future.

Albumin

Albumin, the most abundant colloid molecule in plasma, can be administered through plasma transfusions, canine lyophilized albumin, or concentrated (25%) human albumin. Allogeneic blood products contain approximately 2.5% albumin. The size of the albumin molecule is constant, and the higher the concentration of albumin, the greater the colloid osmotic effect per milliliter of solution. Plasma transfusions have an albumin concentration equal to that of plasma and may not increase intravascular COP significantly when administered as the sole colloid solution. Availability of plasma in an unfrozen form (i.e., liquid plasma) reduces the time to administration; refrigerated liquid plasma is also advocated by some for use during resuscitation of coagulopathic animals.

Because of its high concentration of albumin and high COP (200 mm Hg), 25% human albumin has the greatest capability for increasing plasma COP. When capillary permeability is normal, 25% albumin can be an effective colloid for rapid intravascular volume expansion. It also can be used to minimize interstitial edema in animals with hypoalbuminemia caused by inadequate albumin production or renal and gastrointestinal albumin loss. However, when increased capillary permeability allows plasma albumin to pass into the interstitium, the initial intravascular COP benefits of albumin infusion are temporary and increased interstitial COP and edema may result.

Human albumin has physiochemical properties that differ from canine and feline albumin, and complications appear to occur at a higher rate (about 20%) with human albumin administration in dogs than with allogeneic transfusions. This risk is reduced when the solution is diluted to a 5% concentration with 0.9% saline and administered over 10 to 24 hours. Acute and delayed immune-mediated reactions have been reported after the administration of human albumin, allogeneic plasma, and blood, requiring vigilant monitoring for allergic reactions when any of these colloids are used. Accordingly, these colloids are administered slowly for the first hour, with careful monitoring for adverse reactions, before increasing to standard recommended rates of infusion.

A 5-g lyophilized canine albumin (www.ABRInt.net) recently has been developed for use as a replacement colloid in the treatment of hypoalbuminemia in dogs. It is stored in a dehydrated powder form and reconstituted with isotonic saline to a desired concentration. Information on its clinical use is limited to albumin replacement in dogs with hypoalbuminemia and septic peritonitis, but not for volume replacement.