Synthetic colloids are a combination of water, electrolytes and large molecular weight molecules that contribute to the oncotic force (colloid osmotic pressure, COP) of the intravascular space. Three main types of synthetic colloids are produced: gelatins, dextrans, and hydroxyethyl starches (HES). HES solutions are amylopectin polymers which delay clearance and interfere with breakdown by amylase. Starches are the most frequently used synthetic colloid solutions and are described based on a variety of characteristics. Size is reported as the average molecular weight in Daltons and is the most common descriptor. Molecular weight impacts the rate of renal excretion and allows the molecule to stay within the vessel. It is important to remember that it is the number of colloid particles, not the size, that determines COP. The degree of substitution is the average amount of hydroxyethyl groups occurring at the C2, C3, or C6 carbon positions per glucose residue in the molecule. Higher substitution on C2 imparts greater resistance to amylase degradation and longer persistence in the plasma. In addition to degradation, HES molecules are cleared by renal excretion or tissue uptake. Molecules have been detected in the skin, muscle, kidneys, and intestines more than 12-50 months after intravenous infusion.
Pros of Colloid Administration
The use of colloids to expand intravascular volume, maintain intravascular volume and reduce third spacing may be beneficial in the setting of protein loss, endothelial leakage, or decreased protein production. Colloids may assist in increasing intravascular volume via their contribution to oncotic pressure. A study published by Silverstein et al. (2005) described the efficiency ratio (i.e. the ratio of the increase in blood volume to the amount infused) of various crystalloids and colloids administered to beagles in a randomized crossover design. Both HES and dextrans had an efficiency ratio of approximately 1.0 immediately post-infusion and this ratio increased to approximately 1.4 at 30 minutes post-infusion. By comparison, 0.9% saline had an immediate efficiency ratio of 0.8 that decreased to 0.4 at 30 minutes post-infusion, thus demonstrating the persistent increase in blood volume after synthetic colloid use.
Cons of Colloid Administration
A major concern with starch solutions is their effect on coagulation, acute kidney injury, fluid overload and anaphylaxis. HES has been shown to decrease levels of von Willebrand’s factor and factor VIII beyond those expected by dilution alone and bind to the surface of platelets blocking receptor sites to interfere with fibrin clot stabilization. This effect appears to be most pronounced in HES preparations of higher molecular weights with greater degrees of substitution. This is reflected in the maximal daily dosages listed in Table 1, in which tetrastarch (lowest molecular weight) has the highest recommended limit.
Several large prospective studies or meta-analyses in critically ill people (VISEP, 6S, CHEST, Cochrane Review 2011) raised concern over administration of HES for resuscitation versus crystalloids. These studies found a statistically significant increase in acute kidney injury and need for renal replacement. The plethora of large trials in human medicine has led to the placement of a black box warning by the USDA on HES products stating that HES should not be used in critically ill patients (including those with sepsis) and patients with acute or chronic kidney injury, in addition to a warning related to the risk of bleeding. The European Medicine Agency has suggested that HES should be completely banned. The clinical evidence demonstrating risk of acute kidney injury in veterinary patients has not yet been described.
In summary, there is little evidence proving that synthetic colloids are a superior resuscitation fluid. Unfortunately, large and small molecular weight HES products have been implicated as an intervention that results in increased risk of acute kidney injury and need for renal replacement therapy in people. The author uses 2 – 5 ml/kg tetrastarch boluses as replacement therapy for perioperative hypotension and refractory hypovolemia. Artificial colloid therapy is still utilized when necessary by the author in “at-risk” patients (renal injury, coagulopathy, sepsis), however more conservative doses must be considered to prevent accumulation, given that a “safe” dose range is unknown. Synthetic colloid therapy is discontinued if side effects are noted. Clinicians must evaluate the pros and cons of HES use in veterinary medicine on an individual case basis, as consideration of other resuscitation fluids may be warranted.
About the author
Dr. Stephanie Istvan is a Diplomate of the American College of Veterinary Emergency and Critical Care. She obtained her undergraduate degree in biology from Duke University in 2005 and veterinary medicine degree (VMD) from the University of Pennsylvania School of Veterinary Medicine in 2009. Following graduation from veterinary school, Dr. Istvan completed a one-year rotating internship in small animal medicine and surgery, and a three-year emergency and critical care residency at the North Carolina State University College of Veterinary Medicine in Raleigh, NC. She completed her residency in 2013 and earned board certification that same year. Dr. Istvan served as a critical care specialist in Phoenix, AZ prior to joining VSH in August 2014. Dr. Istvan’s clinical and research interests include transfusion medicine, coagulation, mechanical ventilation and the management of complex, critically ill patients.