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Hydroxyethyl starch - a Debate

Read time: 15 mins
Last updated:13th Mar 2020
Hydroxyethyl starch: the events and studies that have shaped current practices

For over 60 years the safety of hydroxyethyl starch (HES) and its use have been debated, with many physicians arguing that the fluid has serious adverse events and is often misused. The European Medicines Agency (EMA) took the decision to increase restrictions on the use of HES in June 2018, however, some have called for a total ban and feel patient safety is at risk. Controversies around coagulation impairment and tissue storage effects were reported shortly after HES introduction into a clinical setting. Two recent letters to editor by Jon Henrik Laake and Frederico Bilotta, have highlighted the evidence to date and explored the events that have occurred in the build-up to the recent EMA decision (Bilotta et al., 2018; Laake & Møller, 2018). You can see how these events and studies have shaped current views and practices of HES therapy by clicking on the years in the interactive timeline below.

Increasing reports of von Willebrand disease, disseminated intravascular clotting, and histological lesions in patients treated with hydroxyethyl starch (HES) emerged between 1975–2003. 

But this wasn’t the first time the safety of HES had been bought into question, as Alexander et al., detailed in what was described as a quarter-century enigma. 

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Growing research over the concerns of hydroxyethyl starch (HES) as a volume expander highlighted their unsuitability in 2012 in sub-group patient populations, particularly those with severe sepsis. 

The findings of this research caused a stir within the pharmaceutical industry with one manufacturer of HES threatening to take legal action, claiming the findings were incorrect and misleading. 

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The year 2013 began with a large systematic review and meta-analysis reporting no adverse effects or increased mortality in surgical patients receiving tetrastarches, but ended with a contrasting decision made by the European Medicines Agency (EMA) to implement restrictions of hydroxyethyl starch (HES) solutions in patients with sepsis, burns, or who were critically ill.

. Read more about the evidence in the year that shaped this decision and why the evidence on the pro side of the debate may not have been clear-cut as originally suggested. 

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The Europeans Medicines Agency (EMA) was met with a backlash of criticism following the restrictions made in 2013, with a number of experts and academics backing the criticism. 

Evidence supporting the use of hydroxyethyl starch (HES) was also bought into question during 2014. 

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By now those that had criticised the European Medicines Agency’s (EMA’s) decision had gathered support from societies and petitions called for action. 

Possibly the most significant criticism of the decision was also published in 2017 when two studies revealed the staggeringly high percentage of non-adherence to the 2013 restrictions of hydroxyethyl starch (HES) in critically ill patients. 

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Mixed responses came from the European Medicines Agency’s (EMAs) reconsideration of banning hydroxyethyl starch (HES) solutions from the European market, with critics claiming the decision would be based on politics rather than scientific evidence. 

Despite support from a number of international societies and experts, and the EMAs PRAC recommending the proposed ban, the EMA made the decision to continue the marketing of HES under new restrictions, adding to the ongoing debate. 

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