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Limitations of In Vitro Experiments on Hydroxyethyl Starch Solutions

Section Editor(s): Saidman, LawrenceScharbert, Gisela MD; Kozek-Langenecker, Sibylle MD

doi: 10.1213/01.ane.0000270265.36079.2e
Letters to the Editor: Letters & Announcements
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Department of Anesthesiology and Pain Management; Vienna Medical University; Vienna, Austria; sibylle.kozek@meduniwien.ac.at

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To the Editor:

Recently, Boldt et al. (1) compared the antihemostatic effects of two rapidly degradable hydroxyethyl starches (HES) prepared either in a balanced, plasma adapted solution or a saline-based solution. In this in vitro experiment, the balanced HES preparation had less negative effects on rotational thrombelastometry and whole blood impedance-aggregometry than did the saline-based solution. Previous studies employing thrombelastography showed that gross physicochemical characteristics of HES macromolecules (especially molar substitution) significantly modify their side effects on coagulation with rapidly degradable HES having only minimal effects (2). Thus, the likelihood to detect differences between two rapidly degradable HES types dissolved in different carrier solutions appears low.

Nevertheless, the authors report statistically significant differences between balanced and saline-based rapidly degradable HES after progressive in vitro hemodilution of whole blood obtained from only 10 male volunteers. Surprisingly 50% hemodilution resulted in exactly the same values of ADP-induced aggregometry (356 ± 117 AU) for both HES solutions. We question the clinical relevance of the reported difference between the two HES solutions considering that the degree of dilution achieved in bleeding patients ranges below 50%.

In vitro study designs may be inadequate to detect relevant differences in side effects of various HES preparations on coagulation because of the absence of endothelium and compensatory mechanisms such as buffering, control of pH, and electrolyte environment, as well as metabolic degradation. We strongly suggest that adverse coagulation effects of balanced and saline-based HES solutions have to be tested in vivo in patients undergoing surgery with an expected major blood loss. The present experimental in vitro model only shows what happens in this particular model. Calcium, magnesium, and buffer present in the balanced HES solution are likely to enhance aggregation and overall coagulation at high degrees of hemodilution in the test cuvette (3). Both rotational thrombelastometry and impedance-aggregometry are dependent upon platelet count which has been dramatically reduced in this study design.

Gisela Scharbert, MD

Sibylle Kozek-Langenecker, MD

Department of Anesthesiology and Pain Management

Vienna Medical University

Vienna, Austria

sibylle.kozek@meduniwien.ac.at

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REFERENCES

1. Boldt J, Wolf M, Mengistu A. A new plasma-adapted hydroxyethylstarch preparation: in vitro coagulation studies using thrombelastography and whole blood aggregometry. Anesth Analg 2007;104:425–30
2. Kozek-Langenecker S. Effects of hydroxyethyl starch solutions on hemostasis [Review]. Anesthesiology 2005;103:654–60
3. Roche A, James M, Bennett-Guerrero E, Mythen M. Calcium supplementation of saline-based colloids does not produce equivalent coagulation profiles to similarly balanced salt preparations. J Cardiothorac Vasc Anesth 2006;20:807–11
© 2007 International Anesthesia Research Society