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BJA Advance Access published online on February 25, 2005
British Journal of Anaesthesia, doi:10.1093/bja/aei108
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: journal.permissions@oupjournals.org
Accepted January 20, 2005

Laboratory Investigation

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

C. Madjdpour 1, N. Dettori 1, P. Frascarolo 1, M. Burki 2, M. Boll 3, A. Fisch 4, T. Bombeli 5, and D. R. Spahn 1*

1 Department of Anaesthesiology, University Hospital Lausanne, Lausanne, Switzerland
2 Department of Experimental Surgery, University Hospital Lausanne, Lausanne, Switzerland
3 Medical Affairs, B. Braun Melsungen AG, Melsungen, Germany
4 Research Development Liquids, B. Braun Melsungen SA, Crissier, Switzerland
5 Coagulation Laboratory, Division of Haematology, University Hospital of Zürich, Zürich, Switzerland

* To whom correspondence should be addressed.
D. R. Spahn, E-mail: donat.spahn{at}chuv.hospvd.ch


  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 (t1/2{alpha}) 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 (t1/2{beta}), 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; pharmacokinetics; starch, hydroxyethyl.
{ddagger} Declaration of interest. This study was funded in part by B. Braun, of which MB and AF are employees and DS is a paid consultant. B. Braun has funded other research in this department in the past, as have other competitor companies.
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