Safety Information

Trans-Tasman Early Warning System - Alert Communication

Hydroxyethyl starch (Voluven and Volulyte 6%) – review of benefits and risks of harm

Products affected
Information for consumers and caregivers
Information for healthcare professionals
Data summary
What actions are Medsafe taking?
How to report adverse events
Further information

Concerns have been raised regarding an increased risk of death and kidney problems in patients given medicines containing hydroxyethyl starch. These concerns were identified from published clinical studies. Medsafe outlined these concerns in a monitoring communication published during July 2013.

Medsafe and the Medicines Adverse Reactions Committee (MARC) have reviewed the benefits and risks of harms with Voluven and Volulyte 6% in different types of patients.

Medsafe and the MARC concluded that the restrictions already in place for the use of these medicines are adequate to manage the known potential risks of harm.

Voluven and Volulyte 6% should not be used in patients with:

sepsis
severe liver disease
fluid overload
renal failure not related to hypovolaemia (low blood volume)
intracranial bleeding
pre-existing bleeding disorders
known sensitivity to hydroxyethyl starch
pre-existing coagulation or bleeding disorders.

Voluven and Volulyte 6% should only be used in critically ill patients if other fluid replacement measures have been ineffective.

Monitoring communication: Hydroxyethyl starch solutions (Voluven, Volulyte 6%) associated with increased risk of mortality and renal impairment.

Medicines Adverse Reactions Committee minutes of the 158th meeting.

The full restrictions are outlined in the data sheet for Voluven.

The full restrictions are outlined in the data sheet for Volulyte.

Products affected

Voluven and Volulyte 6% are medicines containing hydroxyethyl starch. These medicines are used for fluid replacement (resuscitation) in patients with low blood volume (hypovolaemia). These medicines are also used to ensure maintenance of adequate circulating volume during surgery.

Information for consumers and caregivers

Voluven and Volulyte 6% may be used to replace lost fluid in very ill patients. Alternative medicines include crystalloid solutions such as normal saline (salt water).
Voluven and Volulyte 6% may be used before, during and after surgery as well as in blood loss caused by injuries, to make sure the patient doesn’t become fluid depleted.
These medicines should not be used in patients with severe life threatening infections (sepsis).
These medicines should only be used in critically ill patients if other medicines have not worked.
Speak to your health care professional if you have any concerns about your treatment.

Information for healthcare professionals

Medsafe and the MARC have reviewed the benefits and risks of Voluven and Volulyte 6%.
The available data show that the balance of benefits and risk of harms remains positive when Voluven and Volulyte 6% are used in surgery.
Although the available data indicate that the benefits and risks of Voluven and Volulyte 6% in critically ill patients and those with sepsis are similar to those of crystalloid solutions, Voluven and Volulyte 6% should not be used in patients with sepsis and should only be used in critically ill patients if crystalloids are insufficient.
Renal function should be monitored in all patients receiving Voluven and Volulyte 6%. Treatment with Voluven or Volulyte 6% should be discontinued at the first sign of acute kidney injury.
Report any suspected adverse reactions to the Centre for Adverse Reactions Monitoring (CARM).

Data Summary

The MARC considered that there are differences between hydroxyethyl starches. Therefore in this review only studies using hydroxyethyl starch 130/0.4 (Voluven and Volulyte 6%) were considered. Voluven and Volulyte 6% contain the same hydroxyethyl starch dissolved in different solutions. Data from studies using other starch types as well as Voluven or Volulyte 6% was considered as supportive information.

The CRYSTMAS study¹ provided information on use of Voluven/Volulyte 6% in patients with sepsis. Supportive data was provided by the CRISTAL study² and a sub-analysis of the CHEST study³. The benefits and risks of harm of Voluven/Volulyte 6% were compared with crystalloid and found to be similar. It was noted that there was an imbalance in mortality in the CRYSTMAS study which indicated a preference for using crystalloid treatment.

The CHEST study was the major source of information on the use of hydroxyethyl starch 130/0.4 (the medicine substance contained in Voluven/Volulyte 6%) in critically ill patients. Overall, comparison of the balance of benefits and risks of harm of Voluven/Volulyte 6% with crystalloid solution was very similar. There are some limitations to studies conducted in this patient group meaning that the results of these studies are not definitive.

Review of the benefits and risks of harms in surgical patients used meta-analysis data from a published analysis by Van der Linden⁴ and a sponsor-commissioned meta-analysis. Both analyses showed a positive benefit risk balance when Voluven/Volulyte 6% are used in surgery.

References

Guidet B, Martinet O, Boulain T et al 2012 ‘Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study’ Critical Care 16: R94
Annane D, Siami S, Jaber S et al 2013 ‘Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock. The CRISTAL randomised trial’ JAMA doi:10.1001/jama.2013.280502
Myburgh JA, Finfer S, Bellomo R et al 2012 ‘Hydroxyethyl starch or saline for fluid resuscitation in intensive care NEJM 367: 190-11
Van der Linden P, James M, Mythen M et al 2013 ‘Safety of modern starches used during surgery’ Anesth Analg 116:35-48

What actions are Medsafe taking?

The sponsor will maintain the data sheets for Voluven and Volulyte 6%. Medsafe will re-examine this safety concern if further data becomes available.

How to report adverse events

Online	Submit a CARM report Prescribers can also submit a report using the online reporting tool available in patient management software.
Paper	Download a consumer reporting form (Word Document, 61KB, 1 page) Download a healthcare professional reporting form (PDF, 292 KB, 2 pages) Submit completed forms by emailing CARMreport@health.govt.nz or mail (Medsafe, Ministry of Health, 133 Molesworth Street, Thorndon, Wellington, 6011).
Email	CARMreport@health.govt.nz

Medsafe cannot give advice about an individual's medical condition. If you have any concerns about a medicine you are taking Medsafe encourages you to talk to your healthcare professional.