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Effect of Molecular Weight and Substitution on Tissue Uptake of Hydroxyethyl Starch

A Meta-Analysis of Clinical Studies

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Abstract

Background

Intravenously infused hydroxyethyl starch (HES) can be found in urine, plasma and tissues. HES remaining in plasma and tissues is thought to increase the risk of clinical complications. HES solutions of lower molecular weight and substitution have been developed to increase urinary excretion and reduce plasma persistence. However, their effect on tissue uptake of HES has not been investigated in human subjects.

Objective

Our objective was to test the hypothesis that lower molecular weight and substitution decrease tissue uptake of HES.

Data sources

Computer searches were performed of MEDLINE; EMBASE; the Cochrane Library; meeting abstract databases in surgery, anaesthesiology and intensive care; ClinicalTrials.gov; and Google. Supplementary sources were reference lists and electronic tables of journal contents. No time period or language restrictions were imposed.

Study Selection

Clinical studies were eligible for inclusion in the meta-analysis, if data were reported both for cumulative urinary excretion of HES over 24 hours after infusion and for plasma HES concentration at 24 hours.

Data Extraction

Data were extracted on 24-hour urinary excretion of HES, 24-hour HES plasma concentration, plasma volume, HES molecular weight and substitution, study design, type and demographics of subjects, indication for fluid infusion, and HES infusion regimen. Tissue uptake of HES was computed as the difference between the infused dose and the sum of urinary excretion and residual plasma HES at 24 hours.

Data Synthesis

Twenty-five clinical studies totalling 287 subjects were included. Tissue uptake of low-molecular-weight HES (≤200 kD) was 42.3% (95% confidence interval [CI] 39.6, 45.0) compared with 24.6% (CI 17.8, 31.4) for high-molecular-weight HES (p<0.001). Similarly, tissue uptake of lower-substitution HES (≤0.5) was 42.4% (CI 39.5, 45.3) versus 26.6% (CI 19.6, 33.6) for higher-substitution HES (p<0.001). Among the three most often investigated single HES solutions, tissue uptake of 130/0.4 (42.6%; CI 35.0, 50.2) and HES 200/0.5 (43.3%; CI 39.4, 47.2) closely coincided, whereas uptake of HES 450/0.7 (22.2%; CI 14.8, 29.6) was lower (p = 0.001 and p<0.001, respectively).

Conclusions

This meta-analysis did not support the hypothesis that lower molecular weight and substitution decrease tissue uptake of HES. Further clinical studies of HES tissue uptake are needed.

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Acknowledgements

This meta-analysis was conducted and the paper was prepared with no financial support from any funding organization or sponsor. Professor Wiedermann has received fees for speaking and travel reimbursements from manufacturers of plasma-derived therapies (CSL Behring, Baxter, Kedrion). Professor Bellmann has received research support from Torrex Chiesi and from Pfizer Inc. Doctor Feistritzer declares that he has no potential conflicts of interest that are directly relevant to the content of this article.

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  1. Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria

    Romuald Bellmann & Clemens Feistritzer

  2. Division of Internal Medicine, Central Hospital of Bolzano, Lorenz Böhler Street 5, 39100, Bolzano, Italy

    Christian J. Wiedermann

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  1. Romuald Bellmann
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Bellmann, R., Feistritzer, C. & Wiedermann, C.J. Effect of Molecular Weight and Substitution on Tissue Uptake of Hydroxyethyl Starch. Clin Pharmacokinet 51, 225–236 (2012). https://doi.org/10.2165/11594700-000000000-00000

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