Summary
The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular
weight and the degree of substitution. So far, little attention has been paid to the
clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch.
10 patients with cerebrovascular circulatory disturbance received hemodilution therapy
for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of
substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received
a starch solution with identical initial molecular weight and degree of substitution
but with a C2/C6 ratio of 5.7.
After the administration of a single dose, no significant differences between the
two groups were observed. After repeated administration, significant differences could
be detected in hemorheology, coagulation and elimination (p<0.01). The larger C2/C6
ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in
turn led to a higher increase in serum concentration during the therapy (14.7 vs.8.6
mg/ml). Hematocrit was lowered more (-30,5 vs. -23,5%) and plasma viscosity was increased
more. There was also a more pronounced increase in partial thromboplastin time (+30%
vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex
(p <0.01), which exceeded the dilution effect.
The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After
repeated administration of this starch, large molecules accumulate which are inefficiently
degraded. The same effect has been observed after therapy with highly-substituted
HES. This accumulation of large molecules leads to a beneficial longer lasting volume
effect. The disadvantages include an increase in plasma viscosity and coagulation
disturbances, which cannot be explained with the respective dilution effect alone.
For these reasons, the C2/C6 ratio is of clinical relevance and should be included
in the product labeling in the future.
