PHARMACOLOGY OF LOW-MOLECULAR-WEIGHT HYDROXYETHYLSTARCHES

In the last ten years, the practice of plasma volume expansion has changed significantly. Most clinicans have put a stop to the use of fresh frozen plasma because of growing concerns about hepatitis and AIDS transmission. Today, natural and synthetic colloids and crystalloids are used to a great extent. Although clinical practice varies from one institution to another, the most widely observed change was a major increase in the administration of human serum albumin (HSA). As a result, the cost of plasma volume expansion became so high that it justified finding safe and cheaper alternatives to HSA. Low molecular weight. hydroxyethylstarches (HES) are the synthetic colloids which are closest to HSA. HES are modified natural polymers whose physico-chemical properties are defined by their molecular weight and molar substitution ratio. Average molecular weights of these polydispersed solutions are approximately 200 to 250 kd (in weight) and 60 kd (in number). Hydroxyethylation, which slows down hydrolysis by alpha-amylase, is best quantified by the molar substitution ratio between the proportions of hydroxyethylether and glucose. HES have pharmacokinetic properties which are independent of molecular weight and directly related to the molar substitution ratio. The two HES available in France are Elohes(R) and Lomol(R), Elohes(R). at a concentration of 6%, has a colloid-osmotic effect close to that of plasma. It induces an initial plasma volume expansion greater than that of the infused volume, and has a long lasting effect (24 h) related to its molar substitution ratio (0.62). Lomol , at a concentration of 10% is hyperoncotic. Its initial effect is greater than that of Elohes(R), but it is eliminated more rapidly because its lower molar susbtitution ratio (0.45). The good tolerance to these products is also an advantage in comparison with the other colloids.