Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: Influence of molecular weightand degree of substitution

Objective: To determine the differential influence of molecular weight and the degree of substitution of HES solutions on pharmacodynamics and pharmacokinetics including organ storage in a model of acute hemodilution in pigs. Design: Prospective controlled randomized animal trial. Interventions: After bleeding, 20 ml/kg, animals were substituted with 6% HES preparations (200/0.62, 200/0.5, and 100/0.5). Measurements and results: We did not observe any significant differences in the ability to sufficiently achieve plasma volume expansion and restoration of macrocirculation, nor maintenance of indicators of microcirculation between the groups. Urine production was significantly higher in HES-treated animals and highest in animals substituted with HES 100/0.5. Plasma clearance was measured under steady-state conditions with significantly reduced clearance for the HES 200/0.62 group compared with HES 100/0.5 and HES 200/0.5 (6.6 vs. 13.2 and 13.9ml/min; P ≤ 0.001), thus being dependent on the degree of substitution. Even after only 6 h, the amount of infused HES not detectable in either blood or urine was significantly higher in HES 200/0.62-treated animals (50.7% compared with HES 200/0.5 (28.8%), P = 0.020 and HES 100/0.5 (28.4%), P = 0.018), with its proportion rising over time. Finally, we could demonstrate considerable amounts of all HES solutions being stored in liver, kidney, lung, spleen and lymph nodes. Conclusions: All preparations analyzed sufficiently restored macro- and microcirculation; however, for all solutions relevant tissue storage of HES was observed after only 6 h. Keywords Hydroxyethyl starch * Hemodynamics * Molecular weight * Degree of substitution * Organ storage * Clearance