An international view of hydroxyethyl starches

Abstract

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.

RETRACTED ARTICLE: Le remplissage vasculaire avec de l’HEA 130/0,4 peut réduire la réaction inflammatoire chez des patients en chirurgie abdominale majeure

“…19,20 The hemorheologic effectiveness of HES preparations is determined by their high hemodilutional capacity in combination with their inherent specific effects on platelet function, plasma viscosity, and blood corpuscle-endothelial cell interactions. 21 In a recent clinical study, intravascular volume replacement with HES 130/0.4 improved tissue oxygenation in patients undergoing abdominal surgery. 20 In contrast, equivalent volumes of a crystalloid solution were associated with a marked decrease of tissue oxygen tensions.…”

3.5% urea-linked gelatin is as effective as 6% HES 200/0.5 for volume management in cardiac surgery patients

“…On the one hand gelatin consists of very small molecules, which are rapidly cleared from the circulation by renal filtration, 7 on the other hand, HES is expected to have a prolonged intravascular presence due to its higher in vivo molecular weight. 8 One should, therefore, expect a better plasma volume expansion with HES than with GEL as demonstrated by Mortelmans et al in orthopedic surgery using an albumin marked technique. 12 Several factors may explain our observations.…”

“…According to the available pharmacokinetic data, medium weight hydroxyethyl starches are expected to have a greater plasma expanding effect than gelatins, due to a higher in vivo molecular weight. 7,8 However, few studies have compared these two synthetic colloids in terms of volume expansion in the setting of cardiac surgery. In addition, interpretation of the available clinical data is hampered by a number of methodological issues such as the limited number of patients included, the use of different fluid regimens in the various clinical protocols, and the absence of well-defined endpoints.…”

Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria*

“…Whilst concerns for safety of starches is not new [28], recent evidence suggests that newer generation of medium molecular weight starches such as HES 130/0.4 do not increase the incidence of acute renal failure [29][30][31]. The higher concentration (10%) starches have a higher waterbinding capacity and hence reduced renal flow [32]. In addition, the higher molecular weight pentastarch, but not the medium molecular weight starches, are incompletely metabolised and thus stored in the kidney, the mechanism thought to be responsible for acute renal damage [32,33].…”