Hydroxyethyl Starches

Abstract

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

Effect of Synthetic Colloid Administration on Coagulation in Healthy Dogs and Dogs with Systemic Inflammation

“…Given that tetrastarch administration has no known direct effects on platelet count,3, 4, 10 this suggests a greater hemodilution effect with tetrastarch compared to 0.9% NaCl administration. The blood volume expansion that is achieved with isotonic crystalloids and synthetic colloids differs as administration of the latter produces fluid recruitment from the interstitial compartment 23.…”

“…General indications for colloid therapy include intravascular volume expansion for animals with hypovolemic or distributive shock, as well as animals with hypoalbuminemia and decreased oncotic pressure 1. Adverse effects have been associated with the use of certain synthetic colloids in humans including the induction of coagulopathies, impaired kidney function, and prolonged tissue storage resulting in pruritus 2, 3, 4. Several human studies have compared crystalloids and colloids used during fluid resuscitation, but have failed to identify a survival advantage for either type of fluid 5, 6, 7…”

“…Tetrastarch, a third generation HES, has a smaller molecular weight (MW) and lower degree of molar substitution, thereby exhibiting more rapid elimination and lack of accumulation compared to other HES 4, 8. Reports support a possible lesser impact of tetrastarch on coagulation compared to other larger MW HES products 3, 4, 9.…”

“…Tetrastarch, a third generation HES, has a smaller molecular weight (MW) and lower degree of molar substitution, thereby exhibiting more rapid elimination and lack of accumulation compared to other HES 4, 8. Reports support a possible lesser impact of tetrastarch on coagulation compared to other larger MW HES products 3, 4, 9. Adverse effects of HES on hemostasis in humans are characterized by decreased factor VIII (FVIII) and von Willebrand factor (vWF) activity, dilution of clotting factors, decreased expression of integrin α IIb β 3 on activated platelets leading to decreased aggregation, decreased fibrinogen polymerization, acquired fibrinogen deficiency, and impaired fibrinolysis 3, 4, 10.…”

“…Reports support a possible lesser impact of tetrastarch on coagulation compared to other larger MW HES products 3, 4, 9. Adverse effects of HES on hemostasis in humans are characterized by decreased factor VIII (FVIII) and von Willebrand factor (vWF) activity, dilution of clotting factors, decreased expression of integrin α IIb β 3 on activated platelets leading to decreased aggregation, decreased fibrinogen polymerization, acquired fibrinogen deficiency, and impaired fibrinolysis 3, 4, 10. Studies in vitro and in vivo using thromboelastography (TEG) and similar viscoelastic devices have been performed in humans to evaluate the effect of HES on hemostasis 10, 11, 12.…”