Hydroxyethyl starch intravenous infusions

To be used only in patients with acute blood loss and when crystalloids alone are not sufficient.

From:
Medicines and Healthcare products Regulatory Agency
Published
19 December 2014
Therapeutic area:
Anaesthesia and intensive care

Post-publication note: June 2022.

On 24th May 2022 the European Commission confirmed that the marketing authorisation of hydroxyethyl-starch (HES) solutions for infusion should be suspended. At the time of this decision, no HES products for plasma volume expansion were licensed in the UK.

Hydroxyethyl starch (HES) products are synthetic colloid solutions used for plasma volume expansion. Large randomised clinical trials have reported an increased risk of kidney dysfunction and mortality over 90 days of follow-up in patients who received HES compared with crystalloids.[footnote 1] [footnote 2] [footnote 3] Because of the risks highlighted by these trials, a review of the benefits and risks of HES was started by European regulators in November 2012. The licences of all HES products were suspended in the UK in June 2013,[footnote 4] while the review was on-going.

After considering all the available evidence, the European Medicines Agency concluded that HES should be contraindicated in critically ill patients or patients with sepsis or burns. However, HES can be used in patients with acute blood loss, where treatment with crystalloids alone is not sufficient. As well as new contraindications, HES use will be subject to updated warnings in the information leaflets supplied with HES products.

There is a lack of robust long term safety data in patients undergoing surgical procedures and in patients with trauma. The EU decision requires licence holders to conduct further studies.

The latest NICE clinical guidelines state that tetrastarch should not be used for fluid resuscitation (all HES products licensed in the UK are tetrastarches).[footnote 5] [footnote 6] NICE recommends that crystalloids should be used for intravenous fluid resuscitation.

Advice for healthcare professionals:

  • HES is only indicated for the treatment of low blood volume due to acute blood loss when crystalloids alone are not considered sufficient.
  • Use of HES is contraindicated in:
    • sepsis
    • burns
    • kidney impairment or kidney function replacement therapy
    • intracranial or cerebral haemorrhage
    • critically ill patients (typically admitted to the intensive care unit)
    • hyperhydrated patients, including patients with pulmonary oedema
    • dehydrated patients
    • severe coagulopathy
    • severely impaired liver function
  • The maximum daily dose of HES is 30 ml per kilogram of bodyweight.
  • Only use HES during the first 24 hours of fluid resuscitation treatment.
  • Trauma and surgery: carefully weigh the expected benefit of treatment against the uncertainty of the long term safety of treatment. Consider other available treatment options.
  • Monitor kidney function in patients receiving HES for at least 90 days. Stop HES treatment at the first sign of kidney injury.
  • Stop HES treatment at the first sign of impaired blood clotting.
  • Please continue to report suspected adverse drug reactions to HES or any other medicine via the Yellow Card Scheme

Further information

Letter sent to healthcare professionals in November 2014

Information from the European Medicines Agency

Article citation: Drug Safety Update volume 8 issue 5, December 2014: A3

  1. Brunkhorst F, et al. N Engl J Med 2008; 358: 125–391. ↩

  2. Perner A, et al. N Engl J Med 2012; 367: 124–34. ↩

  3. Myburgh J, et al. N Engl J Med 2012; 367: 1901–11. ↩

  4. Drug Safety Update vol 6, issue 11 June 2013: A1 ↩

  5. NICE guideline CG174: Intravenous fluid therapy in adults in hospital ↩

  6. NICE guideline NG29: Intravenous fluid therapy in children and young people in hospital (reference added after publication) ↩

Published 19 December 2014