Hydroxyethyl starch (HES/HAES), sold under the brand name Voluven among others, is a nonionic starch derivative, used as a volume expander in intravenous therapy. The use of HES on critically ill patients is associated with an increased risk of death and kidney problems.

HES is a general term and can be sub-classified according to average molecular weight, molar substitution, concentration, C2/C6 ratio and Maximum Daily Dose. The European Medicines Agency commenced in June 2013 the process of agreeing to reduced indications which was completed in October 2013. The process of full withdrawal in the EU was expected to complete in 2018.

An intravenous solution of hydroxyethyl starch is used to prevent shock following severe blood loss caused by trauma, surgery, or other problem. It however appears to have greater risk of a poor outcome compared to other intravenous solutions and may increase the risk of death.

HES can cause anaphylactoid reactions: hypersensitivity, mild influenza-like symptoms, slow heart rate, fast heart rate, spasms of the airways, and non-cardiogenic pulmonary edema. It is also linked to a decrease in hematocrit and disturbances in blood clotting. One liter of 6% solution (Hespan) reduces factor VIII level by 50% and will prolong the aPTT and will also decrease vWF. A coagulation effect of hetastarch administration is direct movement into fibrin clots and a dilutional effect on serum. Hetastarch may lead to platelet dysfunction by causing a reduction in the availability of glycoprotein IIb-IIIa on platelets.

HES derivatives have been demonstrated to have increased rates of acute kidney failure and need for renal replacement therapy and to decrease long-term survival when used alone in cases of severe sepsis compared with Ringer lactate solution. The effects were tested on HES 130kDa/0.42 in people with severe sepsis; analysis showed increased rates of kidney failure and increased mortality when compared to LR. It has been recommended that, since medium-MW HES solutions may be associated with harm, these solutions should not be used routinely for patients with septic shock.

During 2010/11 a large number of research papers associated with Joachim Boldt were retracted for ethical reasons, and this may affect clinical guidelines referring to HES preparations prepared before this date. In 2013 a meta-analysis on HES in critically ill patients showed that only the Boldt studies showed an improvement with HES; all other studies showed significant risks with no benefits.

Hydroxyethyl starch has been observed to cause severe pruritis, or itching after administration. This can occur even at doses as low as 400mg/kg cumulative dose, and is considered to be possible at any dose, though does become more common at higher cumulative doses. In a review of the accumulation of hydroxyethyl starch in body tissues, it was found that approximately 15% of patients given the drug had deposits of the drug in their skin. These deposits were more common with higher cumulative doses, and in some cases persisted for 4-8 years or more after last administration. It it thought that the mechanism by which itching is caused is related to deposits of hydroxyethyl starch occurring in peripheral nerves, potentially Schwann cells specifically.

This itching can be very severe and is the most common side effect of hydroxyethyl starch. It generally has a delayed onset of at least a few weeks after administration, which increases the difficulty in diagnosing this side effect as people experiencing itching and their doctors may not consider it as a possible cause. In many patients, it is very difficult or impossible to provide relief from the itching or reduce the duration of the itching. Antihistamines have no effect on itching with this cause. Some small studies or single case reports have suggested potential benefit from oral naltrexone or topical capsaicin, but these have yet to be tested in large trials.