Veterinary Voice, June 2015 – Colloids – To Use or Not?

 

Wendy Yaphe, DVM, Dipl ACVIM

Internal Medicine Specialist

 

Crystalloids vs Colloids – What do they do for us?

Crystalloids are salt containing solutions that contain electrolytes and water in proportions that mimic that of the extracellular fluid in the body. Crystalloids are indicated in the treatment of the patient with fluid deficits – typically the dehydrated or hypovolemic patient.

When crystalloids are given intravenously, they act to immediately expand the vascular volume – but the effect is short-lived and transitory. It is akin to taking a garden hose and trying to fill up a bag with holes in it. The water will stay in the bag for a period of time, but eventually will leak out. Factors that influence how “leaky” the bag is include oncotic pressure (which helps hold fluid in), hydrostatic pressure (which pushes fluid out), and the permeability of the vascular endothelium (vasculitis present?). Albumin is the major colloid in the vascular space and the primary determinant of plasma oncotic pressure.

 

Within one hour of infusion of crystalloids, only 20% remains within the vascular space, and that not excreted by the kidneys moves into the interstitium. Excessive fluid in the interstitium is returned to circulation mostly by the lymphatics and less by diffusion back into blood vessels. As patients continue to receive IV fluids, dependent upon the rate and comorbid conditions (vasculitis, trauma, low albumin), fluids may build up in the interstitium leading to peripheral edema, pulmonary edema, and tissue edema. Accumulation of fluid in the interstitium increases the distance through which oxygen much travel from capillary beds to nourish individual cells, and compromises tissue oxygenation.

 

 

What about colloids – how are they different?

Colloids are solutions that contain large MW molecules in a crystalloid suspension. These large MW molecules also carry a negative charge that results in the attraction of positively charged sodium. Sodium draws water and helps hold it within the vascular space. As the MW of colloids is large, when you pour this solution into the “bag with holes” (eg, the vascular compartment), the molecules are too big (for the most part) to go through the holes, so colloids tend to stay in the vascular compartment much longer than crystalloids, and via their osmotic pull, they attract and hold on to water. These properties make colloids much more effective “volume expanders” with smaller amounts being given. Colloids are particularly beneficial in rapidly restoring blood volume with smaller amounts of infusion, for providing oncotic support to the patient with hypoalbuminemia, and to help maintain fluid within the vascular space in the patient with significant vasculitis.

 

How are colloids excreted?

Colloids are derived from starch and contain a mix of particle sizes. The larger molecules in the vascular compartment are enzymatically broken down by serum amylase. Smaller particles are excreted by the kidneys, or move into the interstitium where they are taken up by cells of the RES to be later degraded. The type of colloid (average molecular weight of particles as well as starch composition) impacts half-life and time to breakdown. Hetastarch (70% molar substitution) is a larger MW colloid (average MW of 430KD), tends to remain in the vascular space longer (approx 36 hrs), and is dosed lower (20 mls/kg/day). Vetstarch (40% molar substitution) is a smaller MW colloid (average MW of 130KD), is degraded more rapidly (average duration in circulation of 4-6 hrs) and dosing (up to 50 mls/kg/day) is higher.

 

How do colloids cause adverse effects?
Deleterious effects linked to colloid use in humans include coagulopathy, acute kidney injury (AKI), and delayed hypersensitivity reactions. Coagulopathic effects are mediated in part by a dilutional coagulopathy, reduced Willebrands and factor VIII activity, and reduced platelet function. The higher MW colloids are more likely to result in adverse coagulation effects. AKI is mediated in part by renal clearance of HES (accounts for 70% of HES elimination). Pinocytosis of HES by proximal tubule cells causes proximal renal tubule cell swelling, altered cellular integrity, and ultimately, renal tubular damage causing AKI.

Secondary routes of HES elimination include movement into the interstitium and

uptake with transient storage in the reticuloendothelial (RES) cells of the liver, spleen, and lymph nodes. HES molecules have also been found in the dermis and nerve cells. HES-asssociated pruritus has been reported in 30-60% of treated humans (not animals) with resultant refractory pruritus that can persist up to 2 years.

 

As a result of studies linking colloid use to the deleterious in humans, the EMA in Europe (equivalent of FDA in USA) pulled HES solutions in 2013, and the FDA posted a black box warning urging caution in use of critically ill patients, including those with sepsis, admitted to the ICU, and avoiding use in patients with pre-existing renal dysfunction.

 

Do the same recommendations apply to our veterinary patients?

It remains controversial as to whether these warnings and concerns should parlay with equivalence to the veterinary patient. Colloids are very unique in the treatment angle that they offer us for the patient that is profoundly hypoproteinemic, has vasculitis, or is in a state of acute life-threatening vascular collapse.

 

Much of the deleterious effects noted in humans would logically transpose to the veterinary world as the physiology between species is more similar vs dissimilar. On the other hand, in the majority of human studies, patients were in ICU units for long times (weeks), had serious co-morbid conditions, and were not a near equivalent to the comparatively shorter and more simplistic ICU stay (average of days) of the acutely ill dog or cat.

 

The choice to use, or not use colloids in the veterinary patient remains controversial for these reasons. The reader is referred to several recent articles in JVECCS for additional insight into this topic.
1. Hydroxyethyl starch: a review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use. JVECCS 2014; 24(6): 642-61

  1. The Crystalloid-Colloid Debate: Consequences of Resuscitation Fluid Selection in Veterinary Critical Care. JVECCS 2015; 25(1): 6–19
  2. Controversies in the use of Hydroxyethyl Starch Solutions in Small Animal Emergency and Critical Care. JVECCS 2015; 25(1): 20-47

 

In the first article, the authors comment “At present there is no veterinary literature or data to support the restriction or cessation of HES product use in small animal veterinary patients”. Ultimately, the decision needs to be made by the individual veterinarian in regards to risk vs benefits of colloid  use, and weighing the individual patient’s best care at the time.

 

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