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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 Feb 20;309(7):678-88. PMID: 23423413

Efficacy Endpoints

Mortality benefit

Harm Endpoints

Mortality, Renal failure

Narrative

Hydroxyethyl starch is a synthetic colloid solution available in various formulations for acute fluid resuscitation. However, its benefit over other solutions has been controversial. It’s been proposed that hydroxyethyl starch and other colloids provide intravascular support using less volume of infusion and have a longer duration of action compared to traditional fluids. Thus, despite challenges with cost and accessibility, it has been included in various resuscitation guidelines.

Recently, hydroxyethyl starch has fallen out of favor given concerns over morbidity and mortality. Also, the data comparing it against other fluids has been an issue of dispute. This review looked at 38 trials enrolling 10,880 subjects, comparing hydroxyethyl starch with other volume expanders (crystalloids, gelatin and albumin) in critically ill patients within emergency departments and intensive care units. The analysis included several studies later retracted secondary to scientific misconduct. When these 7 trials were removed from the data pool, the remaining cohort of 10290 patients showed a slight increase in mortality in the hydroxyethyl starch group (NNH 69, 95% CI 1.02-1.17). The second significant result reported was an increased incidence of renal failure requiring renal replacement therapy (NNH 44, 95% CI 1.15–1.50). There was no difference in length of hospital stay and an increase in red cell transfusion in the hydroxyethyl starch group (NNH 12, 95% CI 1.15-1.75) among the five trials tracking this outcome.

Given the risk of kidney injury, lack of benefit, potential mortality harm, and the general availability of crystalloid solutions, we believe that hydroxyethyl starch should be considered harmful when used as routine replacement for crystalloid fluid.

Caveats

There was high variability between the studies included in this review. Although the most common underlying condition was severe sepsis, the populations studied also included trauma, burn and cardiac arrest patients. The authors also found that the literature was confounded with several trials implicated for scientific misconduct. These studies found no difference in mortality between hydoxyethyl starch and all-cause mortality; when the data from these studies were included, there was no significant difference in mortality (NNH 93, 95% CI 1.00-1.13). Of note, the molecular weight and volume of the starch solutions are said to have an effect on its oncotic properties and it has been suggested that differing solutions could have varying safety profiles. As of yet there is no clinical data to support this notion.

The findings of this review for effects of a specific colloid (hydroxyethyl starch) are consistent with those of our previous review on the subject of colloid solutions (in general) for resuscitation in critically ill patients. However, we feel that despite the heterogeneity, in the case of this specific agent, the cost, clear lack of benefit and the significant potential harms warrant a rating of Black.

Author

Christina Chao, MD

Published/Updated

April 17, 2013