Intensive Care Medicine

, Volume 40, Issue 2, pp 160–170 | Cite as

Accumulation of hydroxyethyl starch in human and animal tissues: a systematic review

  • Christian J. Wiedermann
  • Michael Joannidis
Systematic Review



To systematically review clinical and preclinical data on hydroxyethyl starch (HES) tissue storage.


MEDLINE (PubMed) was searched and abstracts were screened using defined criteria to identify articles containing original data on HES tissue accumulation.


Forty-eight studies were included: 37 human studies with a total of 635 patients and 11 animal studies. The most frequent indication for fluid infusion was surgery accounting for 282 patients (45.9 %). HES localization in skin was shown by 17 studies, in kidney by 12, in liver by 8, and in bone marrow by 5. Additional sites of HES deposition were lymph nodes, spleen, lung, pancreas, intestine, muscle, trophoblast, and placental stroma. Among major organs the highest measured tissue concentration of HES was in the kidney. HES uptake into intracellular vacuoles was observed by 30 min after infusion. Storage was cumulative, increasing in proportion to dose, although in 15 % of patients storage and associated symptoms were demonstrated at the lowest cumulative doses (0.4 g kg−1). Some HES deposits were extremely long-lasting, persisting for 8 years or more in skin and 10 years in kidney. Pruritus associated with HES storage was described in 17 studies and renal dysfunction in ten studies. In one included randomized trial, HES infusion produced osmotic nephrosis-like lesions indicative of HES storage (p = 0.01) and also increased the need for renal replacement therapy (odds ratio, 9.50; 95 % confidence interval, 1.09–82.7; p = 0.02). The tissue distribution of HES was generally similar in animals and humans.


Tissue storage of HES is widespread, rapid, cumulative, frequently long-lasting, and potentially harmful.


Hydroxyethyl starch Hetastarch Storage Accumulation Uptake Deposit 


Conflicts of interest

CJW received fees for speaking and travel cost reimbursement from CSL Behring, Baxter, Kedrion, and the Plasma Protein Therapeutics Association, an organization representing the private sector manufacturers of plasma-derived and recombinant analogue therapies including albumin. MJ received speaker’s honoraria from Baxter, Fresenius, Gambro, Orion Pharma, CLS Behring, and Braun Melsungen.

Supplementary material

134_2013_3156_MOESM1_ESM.doc (52 kb)
Supplementary material 1 (DOC 52 kb)


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© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  1. 1.Department of Internal MedicineCentral Hospital of BolzanoBolzanoItaly
  2. 2.Division of Emergency and Intensive Care Medicine, Department of Internal MedicineMedical University of InnsbruckInnsbruckAustria

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