Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation: A Systematic Review and Meta-Analysis

Study Questions:

What is the impact of using hydroxyethyl starch for volume resuscitation on patient outcomes?


The authors performed a systematic review and a meta-analysis of all randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation.


The authors identified 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The use of hydroxyethyl starch was associated with a trend toward increased risk of death (risk ratio [RR], 1.07; 95% confidence interval [CI], 1.00-1.14; I2, 0%). This summary effect measure included results from seven trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. After exclusion of these seven trials, hydroxyethyl starch was associated with increased mortality (RR, 1.09; 95% CI, 1.02-1.17), increased renal failure (RR, 1.27; 95% CI, 1.09-1.47), and increased use of renal replacement therapy (RR, 1.32; 95% CI, 1.15-1.50).


The authors concluded that use of hydroxyethyl starch for volume resuscitation is associated with an increased risk of death and renal failure.


This study highlights the deleterious impact of using hydroxyethyl starch for volume resuscitation in critically ill patients. This review also highlights the harmful impact of academic misconduct on clinical care. Most high-quality studies had raised concerns about the renal toxicity of hydroxyethyl starch (see Cittanova ML, et al. Lancet 1996;348:1620-2), but until the retraction of the work by Boldt, there was greater ambiguity about the safety of this agent. Based on the safety concerns highlighted in this study, the use of hydroxyethyl starch needs to be avoided.

Keywords: Hydroxyethyl Starch Derivatives, Renal Insufficiency, Resuscitation, Fluid Therapy, Acute Kidney Injury, Critical Illness, Isotonic Solutions, Renal Replacement Therapy

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