The starch family: are they all equal? Pharmacokinetics and pharmacodynamics of hydroxyethyl starches

Abstract

SUMMARYWith the third generation of hydroxyethyl starches (HES), this product group has again moved into the focus of scientific interest. The pharmacodynamic action of HES as a colloid depends on the number of oncotically active molecules but not directly on the plasma concentration, while effects on blood coagulation, especially on factor VIII and von Willebrand factor, depend on plasma concentration and in vivo molecular weight. HES with a molar substitution above 0.4 tends to accumulate in plasma after repetitive infusion. This effect is most pronounced with hetastarch (e.g. HES 670/0.75) and corresponds to the extent of tissue storage, which is significantly reduced for HES 130/0.4 compared with hetastarch and HES 200/0.5. HES 130/0.4 does not accumulate in plasma after repetitive administration, and plasma clearance of HES 130/0.4 is more than 23 times higher than that of hetastarch. This is beneficial especially in patients with preexisting renal insufficiency, as cumulative urinary excretion, even in the presence of moderate to severe non‐anuric renal failure, is higher for HES 130/0.4 than for older HES specifications when given to healthy volunteers. No adverse effects on kidney function have been observed for HES 130/0.4 compared with gelatin in patients with preoperative renal impairment undergoing aortic surgery. Based on recent study results, HES 130/0.4 may be given to patients with renal impairment as long as urine flow is preserved. The volume effect induced by HES does not directly mirror pharmacokinetics. Equivalent volume efficacy has been proven for HES 130/0.4 versus HES 200/0.5 and HES 670/0.75 despite longer intravascular persistence of the less metabolizable HES products. Influence on coagulation is minimal with HES 130/0.4. Recent clinical data showed reduced blood loss and RBC transfusion requirements when comparing HES 130/0.4 (C2/C6 > 8) with hetastarch and pentastarch. HES 130/0.4 combines the advantages of an efficacious volume therapeutic registered for high‐dose treatment with a significantly improved safety profile.