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Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis: a systematic review

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Abstract

Purpose

Hydroxyethyl starch solutions (HES) are plasma volume expanders which affect hemostasis. Newer HES 130/0.4 is said to be safer. Reevaluation of published evidence is necessary after the recent retraction of studies.

Methods

Systematic review of studies assessing HES 130/0.4 effects on hemostasis by thrombelastography (TEG, ROTEM) or Sonoclot (SCR) in comparison with crystalloid or albumin control fluids was performed. Only studies which provided statistical comparisons between study fluids were analyzed. Studies were divided into in vitro or in vivo hemodilution studies. We assessed study quality, HES effects which differed significantly from controls, values outside normal range, degree of hemodilution, and cumulative HES dose.

Results

Seventeen in vitro and seven in vivo hemodilution studies were analyzed. Four studies reported quality control measures.

Nineteen studies (all 15 ROTEM studies, 3 of 5 in vitro TEG, and 1 of 2 SCR studies) showed a significant hypocoagulatory effect of HES 130/0.4 on clot formation, while clotting time was not uniformly affected. Three in vivo TEG studies with low HES doses or cancer patients found mixed or nonsignificant results. In studies which provided normal ranges (n = 9), more values were outside normal ranges in the HES than in the control groups (87/122 vs. 58/122, p < 0.001). Dose effects were apparent in the in vitro studies, which investigated higher dilutions up to 80%. In vivo studies were fewer and did not investigate doses >40 ml/kg.

Conclusions

HES 130/0.4 administration results in a weaker and smaller clot. Until results from well-designed clinical trials are available, safer fluids should be chosen for patients with impaired coagulation.

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Acknowledgments

The authors gratefully acknowledge the contributions of Dr. Shasha Chen for Chinese language translation and of Prof. Don Bredle for English language editing. Support was provided solely from institutional and/or departmental sources.

Conflict of Interest

C.S.H. and D.R. declare no conflicts of interest. W.L. has in the past received study support, honoraria, and travel funding from CSL Behring, Germany and Pentapharm Germany. M.H. received speaker fees and travel costs from CSL Behring. K.R. has in the past received consultancy fees from B. Braun Melsungen.

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Authors and Affiliations

  1. Department for Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany

    Christiane S. Hartog, Dorit Reuter, Wolfgang Loesche, Michael Hofmann & Konrad Reinhart

  2. Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany

    Konrad Reinhart

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  1. Christiane S. Hartog
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  2. Dorit Reuter
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  3. Wolfgang Loesche
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  4. Michael Hofmann
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Correspondence to Konrad Reinhart.

Additional information

C. S. Hartog and D. Reuter contributed equally to this work.

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Appendix

Appendix

Electronic search strategy

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Search

1:

visco elastic or thrombelastography or thrombelastometry or ROTEM or ROTEG or Sonoclot or TEG.

2:

hextend or hespan or “hydroxyethyl starch” or hetastarch or pentaspan or hemohes or pentafraction or expafusin or voluven or tetrastarch or haes steril or elohes or elohaes or plasmasteril

3:

animals not human

4:

1 and 2

5:

4 not 3

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Hartog, C.S., Reuter, D., Loesche, W. et al. Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis: a systematic review. Intensive Care Med 37, 1725–1737 (2011). https://doi.org/10.1007/s00134-011-2385-z

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