Hydroxyethyl starch intravenous infusion: suspension of licences

Clinical trials have reported an increased risk of renal dysfunction and mortality in critically ill or septic patients who received hydroxyethyl starch (HES) compared with crystalloids.

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

Article date: June 2013

This article has been superseded. Please see the article published in December 2014 for the latest advice.

Hydroxyethyl starch (HES) products are synthetic colloid solutions used for plasma volume expansion in a range of clinical settings. In the UK, marketed HES products are: Volulyte; Tetraspan; Venofundin; and Voluven.

Large randomised clinical trials have reported an increased risk of renal dysfunction and mortality over a 90-day follow-up in patients who received HES compared with crystalloids. Increased risk of renal dysfunction has been shown in trials of patients with sepsis[footnote 1] [footnote 2] and in a large trial of critically ill patients, including a subgroup with sepsis. [footnote 3] Increased mortality at 90 days was also shown in the trials of patients with sepsis. 1,2

The most accurate estimate of the magnitude of these risks is from meta-analyses of published data. A meta-analysis published in JAMA reported an increased relative risk of renal failure of 1•27 (95%CI 1•09–1•47) for HES compared with crystalloid.[footnote 4] A Cochrane review that included 25 studies with mortality data reported an increased relative mortality risk of 1•10 (95%CI 1•02–1•19) for HES compared with crystalloid.[footnote 5]

The EU Pharmacovigilance Risk Assessment Committee has reviewed the balance of benefits and risks of HES products in different patient groups. The review concluded that there is a clear indication of harm when HES is used for fluid resuscitation, and no evidence of a greater benefit, compared with crystalloid solutions. The risks HES products pose to patients are considered to outweigh the benefits in all clinical settings. Although a formal EU regulatory position has not been finalised, on the advice of the Commission on Human Medicines, the licences and therefore use of HES products is being suspended in the UK.

$CTA Advice for healthcare professionals:

  • there is clear evidence of harm from increased renal dysfunction and mortality associated with the use of HES, and overall the risks outweigh the benefits
  • there is no evidence that infusion solutions containing HES for plasma volume expansion provide additional clinically relevant benefit to patients compared with crystalloids in any indication
  • HES should not be used for plasma volume expansion. An alternative resuscitation fluid should be selected according to clinical guidelines
  • a recall of all remaining HES stock has been issued

Further information

Information from the European Medicines Agency

Article citation: Drug Safety Update vol 6, issue 11 June 2013: A1

  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. Zarychanski R, et al. JAMA 2013; 309: 678-88 ↩

  5. Perel P, et al. Cochrane Database Syst Rev 2013; 2: CD000567. ↩

Published 11 December 2014