Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?

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Serval ID
serval:BIB_BBF95D7BBEE4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?
Journal
British Journal of Anaesthesia
Author(s)
Madjdpour C., Dettori N., Frascarolo P., Burki M., Boll M., Fisch A., Bombeli T., Spahn D.R.
ISSN
0007-0912 (Print)
ISSN-L
0007-0912
Publication state
Published
Issued date
2005
Volume
94
Number
5
Pages
569-576
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
BACKGROUND: The development of hydroxyethyl starches (HES) with low impact on blood coagulation but higher volume effect compared with the currently used HES solutions is of clinical interest. We hypothesized that high molecular weight, low-substituted HES might possess these properties.
METHODS: Thirty pigs were infused with three different HES solutions (20 ml kg(-1)) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa). Serial blood samples were taken over 24 h and blood coagulation was assessed by Thromboelastograph analysis and analysis of plasma coagulation. In addition, plasma concentration and in vivo molecular weight were determined and pharmacokinetic data were computed based on a two-compartment model.
RESULTS: Thromboelastograph analysis and plasma coagulation tests did not reveal a more pronounced alteration of blood coagulation with HES 500 and HES 900 compared with HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1 (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100) to 381 (63) min].
CONCLUSIONS: In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect.
Keywords
Blood Coagulation/drug effects, Blood Viscosity/drug effects, Hydroxyethyl Starch Derivatives/blood, Hydroxyethyl Starch Derivatives/chemistry, Hydroxyethyl Starch Derivatives/pharmacology, Plasma Substitutes/chemistry, Plasma Substitutes/pharmacokinetics, Plasma Substitutes/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
13/07/2018 10:00
Last modification date
01/10/2019 7:19
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