Page 667 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

654 SPECIAL THERAPY

of the solution. The polydispersity index can be calculated smaller average molecular weights, including pentastarch
from the ratio of the weight average to the number aver- (HES 200/0.5) and HES 130/0.4 (Voluven, Fresenius
age for that solution. Hydroxyethyl starch with a weight Kabi). These lower molecular weight products have been
average molecular mass of 100 to 300 kDa seems to pro- developed to maximize volume expansion effects while
vide the best compromise between colloid osmotic vol- minimizing the risk of adverse effects on the hemostatic
ume expansion and duration of action. 40 Furthermore, system by reducing the number of large molecules. The
this size distribution has less effect on coagulation 164 FDA recently approved Voluven for use in the United
and is the best size for reducing the increases in perme- States.
ability present in patients with vascular leaks. 184 Albumin, obtained from purified human plasma, has
been used to provide colloid support in human medicine
Degree of Substitution and Molar for many years. Albumin most commonly is given to small
Substitution Ratio animal patients as stored or fresh frozen plasma, stored
The amylopectin may be hydroxyethylated at carbons 2, whole blood, or fresh whole blood. Human serum albu-
3, or 6 of the constituent glucose molecules. The degree of min has been used in small animal patients and a canine
substitution is determined by measuring the number of serum albumin preparation has recently become available.
substituted glucose molecules and dividing this by the Albumin has a molecular weight of approximately 69 kDa
total number of glucose molecules present. In contradis- and a molecular radius of 3.5 nm. It is a monodisperse
tinction, the term substitution ratio or more correctly colloid (i.e., all albumin molecules are the same size).
“molar substitution ratio” may also be used and refers In addition to its role in maintaining plasma COP, it car-
to the total number of hydroxyethyl groups present ries a wide range of substances such as bilirubin, fatty
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divided by the quantity of glucose molecules. Although acids, metals and other ions, hormones, and drugs.
not identical, the terms are often used interchangeably Albumin equilibrates with the interstitial space more rap-
with the degree of substitution being used most com- idly and to a greater extent than artificial colloids, and rel-
monly in product descriptions. A higher degree of substi- atively large volumes must be given to achieve a sustained
tution prolongs intravascular persistence by slowing increase in plasma COP. In human medicine, a large trial
down the rate of hydrolysis (i.e., those products with a comparing fluid resuscitation of critical patients with
high degree of substitution will have longer persistence either saline or albumin found no significant differences
in the body). “Hetastarches” have the most between the groups in a number of variables, including
hydroxyethylation (between 0.6 and 0.7), 28-day outcome. 60 The authors of the study concluded
“pentastarches” a degree of substitution of 0.5, and that decisions about which fluid to use should be based
“tetrastarches” a degree of substitution of 0.4. on clinician preference, possible adverse effects, and cost.
Although administration of human albumin solutions to
C2/C6 Ratio critically ill dogs has been associated with effective
The hydroxyethylation can occur at carbons in position 2, increases in serum albumin concentration, refractometric
3, or 6 of the glucose unit. Individual glucose molecules total solids, and COP with relatively few adverse
can have from zero to three hydroxyethyl groups. Hydro- effects, 32,167 administration to healthy animals has been
lysis by amylase is slowed more by substitution at C2 as associated with serious adverse outcomes. 36,61
opposed to C6, 166 thus those products with a high When considering chronic albumin supplementation,
C2/C6 ratio will be metabolized more slowly and intra- as opposed to acute volume expansion, the amount of
vascular volume expansion will be expected to be longer. albumin required can be estimated using an equation that
Hydroxyethylation at the C2 position confers greater corrects for the expected volume of distribution across
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resistance to degradation than the C6 position. the intravascular and interstitial spaces :
Hydroxyethyl starches are thus generally characterized
by their weight average molecular weight, substitution Albumin deficit ðgÞ¼ 10 ½desired albuminðg=dLÞ
ratio, and C2/C6 hydroxyethylation ratio. 163 Hespan, patient albuminðg=dLފ body weightðkgÞ 0:3
for example, has an average molecular weight of 450
kDa and a substitution ratio of 0.7 and therefore is
To increase the serum albumin concentration from
referred to as HES 450/0.7. Two forms of high molecu-
1.5 g/dL to 2.5 g/dL in a 20-kg dog:
lar weight hydroxyethyl starch are available in the United
States, HES 450/0.7 (Hespan, Teva, Irvine, Calif.) and
Albumin deficit ¼ 10 ð2:5 1:5Þ 20 0:3 ¼ 60 g
Hextend (Hospira, Lake Forest, Ill.), which have a weight
average molecular weight of 670 kDa, a molar substitu-
tion of 0.75, and a high C2/C6 ratio. In many European This amount is equivalent to 2 L of plasma or 4 L of fresh
countries and Australia, the high molecular weight whole blood and does not take into account ongoing
starches are no longer available. Several hydroxyethyl losses. Hence, administration of albumin in plasma is
starch products are available in these countries with an inefficient means of providing colloid support.