Summary Safety Review - Hydroxyethyl Starch Solutions - Risk of Kidney Injury and Death
Review decision
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Issued: 2014-12-03
issue
A safety review was initiated to evaluate the currently available information regarding the possible increased risk of kidney injury and death associated with hydroxyethyl starch (HES) solutions when compared to alternative treatments. This review was prompted by the publication of three studies (Perner et al, 2012; Brunkhorst et al, 2008; Myburgh et al, 2012) whose results indicated an increased risk of kidney injury and death associated with HES solutions.
Background
Approved use of HES solutions in Canada
HES solutions are used for treating low blood volume. They work by increasing the amount of fluid in circulating blood. At the time of this review, 3 HES solutions were marketed in Canada: VOLUVEN, VOLULYTE, and PENTASPAN. HEXTEND, another HES product, was approved at the time of this review but it was no longer being marketed.a
Risk of kidney injury and death
Kidney injury refers to a decrease or loss of kidney function, which can lead to a number of complications. In advanced cases, kidney replacement therapy, such as dialysis to filter the blood, may be needed to replace certain functions typically performed by a healthy kidney.
This review also assessed evidence regarding the possibility of death (for any reason), as an overall measure of safety.
Objective
To assess the available evidence concerning the increased safety risks associated with the use of HES solutions in comparison to alternative treatments. This review considered Canadian adverse reaction reports, scientific and medical literature, and international safety data, as well as what is known about the use of these products both in Canada and internationally.
Key findings
Use of HES solutions in Canada
HES solutions are used in hospitals and in other emergency settings where treatment for low blood volume may be required.
Canadian reports of all adverse reactions associated with the use of HES solutions
At the time of this review, Health Canada had received 28 reports of adverse reactions suspected of being associated with HES solutions. In general, reports lacked important details regarding the health of the patient at the time the HES solution was given, as well as the amount of HES that was administered. The most commonly reported side effect was a blood clotting disorder (coagulopathy). This is a well-known side effect which is described in the prescribing information for these products. Among the 28 reports, there was one case of kidney failure and one case of death involving a blood clotting disorder.
Scientific reports and international data
Data from 3 published studies showed an increased risk of kidney injury or death requiring kidney replacement therapy in patients receiving HES solutions in comparison to alternative treatments. These studies involved critically ill patients, including patients with a severe blood infection called sepsis. These findings were supported by 3 additional published analyses (Haase et al, 2013; Perel et al, 2013; Zarychanski et al, 2013) that took into consideration a large volume of related literature on this subject (meta-analyses).
Conclusions and actions
Health Canada has completed its review of the available safety information and has found that there is an increased risk of kidney injury and death in critically ill patients, including patients with a severe blood infection (sepsis), who are treated with HES solutions.
Health Canada actions:
- Health Canada has communicated on the increased risk of kidney injury and death associated with currently marketed HES solutions, VOLUVEN and VOLULYTE, to both patients and healthcare professionals on June 24, 2013 and July 18, 2013, respectively.
- Health Canada has worked with the manufacturer of VOLUVEN and VOLULYTE to update the prescribing information of these products to indicate that they should no longer be used in patients with sepsis. The prescribing information has also been updated to include warnings on the increased risk of kidney injury requiring kidney replacement therapy and death in critically ill adult patients, and recommendations to (a) avoid use in patients with pre-existing kidney problems, (b) discontinue the product at the first sign of kidney injury and (c) monitor kidney function.
References
- Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012;367(2):124-34.
- Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358(2):125-39.
- Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367(20):1901-11.
- Haase N, Perner A, Hennings LI, et al. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 2013;346:f839.
- Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;2:CD000567.
- Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013;309(7):678-88.
Footnotes
- HEXTEND and PENTASPAN were discontinued in Canada, as of July 12, 2013 and November 8, 2013, respectively.
- This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review.