Hydroxyethyl starch: A half‐century enigma

We read with great attention the position statement by Laake JH et al, on behalf of the Board of the Scandinavian Society of Anaesthesiology Intensive Care Medicine in support of the suspension of the use of the hydroxyethyl starch (HES) as proposed by European Medicines Agency (EMA). Of interest, the controversy on safety of plasma expanders, including HES, dates back to the mid 1970s when it was already defined “a quarter century enigma” and is still puzzling today. Here, we focus on the latest decision from EMA on the use of HES and on the implementation of restrictions prescribed by regulatory agencies over‐time. The market authorisation for HES has recently been evaluated by EMA authority. This action was required in October 2017 by the Swedish Medical Products Agency under procedure 107i (“...triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue”) in consideration of the alarming findings on HES utilisation recorded in a dedicated survey in European countries. Data on HES use were collected in a 10‐month observation period in 11 European countries and showed: “(...)non‐adherence to revised product information — prescribed in 2013 by EMA— was reported to range from 67% to 77%, including 20%‐34% non‐adherence to contraindications”. In January 2018, EMA‐PRAC recommended to suspend marketing authorisations for HES solutions “(...)in view of the serious risks that certain patient populations are exposed to(...)”. This recommendation was subsequently confirmed by EMA's Coordination Group for Mutual Recognition and Decentralised Procedures in Humans (CMDh): “(...)due to serious risks of kidney injury and death in certain patient populations(...)”. The EMA‐ PRAC and EMA‐CMDh recommendation to suspend HES market authorisation in Europe gave rise to opposite reactions: the support from the Scandinavian Society of Anaesthesiology Intensive Care Medicine together with the national societies of Iceland, Denmark, Finland, Sweden, and Norway and from an international group of scientists. On the other hand, there was an opposition from Zwißler B —the President of the German Society of Anaesthesiology and Intensive Care (DGAI)— and from French, Spanish, and Czech anaesthesia national societies that claimed possible “unmet medical need” (not supported by specific evidence). This led the European Commission (EC), called to make a legally binding decision, to request PRAC and CMDh to re‐evaluate their recommendations. In May 2018, EMA‐PRAC confirmed the recommendation to suspend HES derived products as delivered in January 2018. In June 2018, the EMA‐CMDh did not confirm the decision to suspend HES but delivered new restrictive rules: “HES solutions for infusion should remain on the market provided that a combination of additional measures to protect patients is implemented.(...).” The new measures are: