Safety and Efficacy of HES for Fluid Resuscitation in the ICU

Greg Martin, MD


January 10, 2013

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care

Myburgh JA, Finfer S, Bellomo R, et al
N Engl J Med. 2012;367:1901-1911


Colloids are is widely used for fluid resuscitation in critically ill patients, but despite newer formulations developed to improve the safety of synthetic starches, such as hydroxyethyl starch (HES), their safety and efficacy have not been completely established.

For patients with sepsis, there are recommendations to use either colloids or crystalloids for fluid resuscitation,[1] yet prior studies have shown that HES may cause acute kidney injury in these patients.[2,3] The authors of this study sought to determine the safety and efficacy of HES for fluid resuscitation in a more general population of critically ill patients, particularly with respect to survival and renal function. They randomly assigned 7000 intensive care unit (ICU) patients to receive either 6% HES in 0.9% sodium chloride (130/0.4, Voluven®; Fresenius Kabi) or 0.9% sodium chloride alone (normal saline) for all fluid resuscitation during the ICU stay until either ICU discharge, death, or 90 days after randomization.

There was no difference in the number of subjects who died at 90 days (18.0% HES and 17.0% saline; P = .26) and there was no difference in mortality in 6 predefined subgroups. Renal injury (by RIFLE criteria) occurred in 34.6% and 38.0% of patients (P = .005), respectively, while renal failure occurred in 10.4% and 9.2% of patients (P = .12). Renal replacement therapy was used more commonly in HES patients (7.0% vs 5.8%; relative risk = 1.21; P = .04), and HES was associated with more adverse events (5.3% vs 2.8%; P < .001). The authors concluded that there is no difference in 90-day mortality between ICU patients resuscitated with 6% HES or saline but that more HES patients were treated with renal replacement therapy.


Ever since earlier studies suggested adverse effects with starch administration,[2] and the retraction of a large number of studies published by one investigator for fraud,[4] there has been increasing scrutiny of both the safety and efficacy of the use of starch in fluid resuscitation in critically ill patients. It was thought that the newer generation of starch products, particularly this generation with a lower molecular weight, would result in fewer instances of kidney failure. The VISEP study subsequently demonstrated that 10% HES caused increased rates of kidney injury, which had a dose-related influence on increasing mortality.[3]

The VISEP study was followed by the Scandinavian 6S trial, which also found serious and similar adverse effects associated with a newer-generation starch solution.[5] Because these findings of various similar starch solutions are also similar, it seems that the effect of starches on kidney injury is a class effect. With this current state of knowledge regarding synthetic colloids, starch solutions should be avoided in critically ill patients, particularly those with acute inflammatory responses such as severe sepsis and septic shock.[6] These results apply specifically to starch solutions and not necessarily to other synthetic or natural colloids, which have been associated with either safety or even improved outcomes in septic shock. Additional data should be collected to further explore starch safety and efficacy, but this should be done only in the context of rigorous clinical trials.