Would the colloid detractors please sit down!
The preferred volume expander in patients with sepsis and SIRS remains controversial, with no conclusive data demonstrating that the type of resuscitation fluid has a major impact on outcome (5). Advocates of colloids argue that hypo-oncotic crystalloids leak from the plasma to excessively expand the interstitial fluid volume, whereas crystalloid supporters argue that leakage of colloid into the interstitial space contributes to edema formation. Nevertheless, it has been suggested that a colloid solution that remains intervascular, is biodegradable, and has a short half-life would be the ideal volume expander in patients with “leaky capillaries.” How do the hydroxyethyl starch (HES) solutions match up to this idealized volume expander?
HES is synthesized from amylopectin, a starch derived from maize or sorghum. It consists of D-glucose units linked in a branching structure. A reaction between ethylene oxide and amylopectin in the presence of an alkaline catalyst attaches hydroxyethyl to the glucose moieties. These hydroxyethyl groups retard hydrolysis of the compound by amylase, thereby delaying its breakdown and elimination from the blood. The degree of substitution (expressed as a number between 0 and 1) indicates the fraction of glucose moieties bearing a hydroxyethyl group. The degree of substitution can be controlled by varying the reaction duration, whereas the size of the molecules can be modified by acid hydrolysis of the parent compound. HES solutions are polydisperse, containing a range of molecular weights. A higher molecular weight range (eg, 450,000 vs. 200,000) and a more extensive degree of substitution (eg, 0.7 vs. 0.5) results in a slower elimination. Hespan (Dupont Pharma, Wilmington, DE) is the only commercially available HES solution in the United States. Hespan (HES 450/0.7) has a degree of substitution of 0.7 (7 hydroxyethyl groups/10 glucose units), a number average molecular weight (Mn; sample mass in grams divided by the total number of molecules) of 60–80 kDa, and a weight average molecular weight (Mw; the sum of each molecule’s weight divided by the sample weight × the weight of the molecule) of 450 kDa. Hespan as prepared for clinical use consists of 6 g HES/100 mL of normal saline and has an osmolarity of 310 mOsm/L. Several HES fractionation products have been developed on the premise that they have the ability to selectively “seal” the endothelial pores that develop in the microvasculature after different forms of injury. Examples of these compounds are pentastarch (Mw, 280 kDa; Mn, 120 kDa) and pentafraction (Mw, 264 kDa; Mn, 63 kDa). Both compounds have a substitution ration of 0.5. The effects of HES on intravascular volume usually last 24 hrs (6). The major route of elimination of HES is by renal excretion. HES polymers <59 kDa are eliminated almost immediately by glomerular filtration.