Post-transfusion survival of hydroxyethyl starch 450/0.70 in man: a long-term study

Intravascular persistence concomitant with changes occurring in the circulating molecular size distribution were determined in five healthy normovolaemic men dosed with 7 ml/kg of a 6% (w/v) solution of a species of hydroxyethyl starch (HES 450/0.70) possessing a M(w)- of 450 000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0.70 (70 hydroxyethyl groups/100 glucose residues). The concentration of HES 450/0.70 in serum fell to 24% of its peak value (measured 2 minutes post injection) one week after the infusion. By 17 weeks after injection, < 1.0% remained in the intravascular space. The HES 450/0.70 material recovered from the bloodstream 2 minutes after injection was shown by gel filtration on a column of Sepharose CL-4B to be less polydisperse than the injected solution. The K(av) calculated for the peak of material eluted after one week showed a definite shift of molecular size toward that of a lower molecular weight composition. However, at four weeks the value of K(av) indicated a shift toward the high molecular weight region of the injected solution, and by seven weeks this movement was quite pronounced. These data clearly indicate the complex nature of the removal of HES 450/0.70 from the intravascular space of man and appear to substantiate previous clinical studies reporting that the MS plays the major role influencing the rate of elimination of this material from the bloodstream.