In an analysis of studies that examined critically ill patients requiring an increase in blood fluid volume, intravenous use of the fluid hydroxyethyl starch, compared with other resuscitation solutions, was not associated with decreased mortality and was associated with a significant increased risk of death and acute kidney injury, according to an article appearing in the Feb. 20 issue of JAMA.
Clinical trials on hydroxyethyl starch, made by Fresenius SE, have lead to conflicting data, and multiple trials from one key investigator have been retracted because of scientific misconduct, including a failure to acquire ethical approval for research and fabrication of study data, the researchers said. "The effect of these retractions has been far-reaching," the study authors wrote. "All major systematic reviews and clinical guidelines are now being revised to account for the retracted data and permit sensitivity analyses on the remaining publications by Boldt et al."
Ryan Zarychanski, MD, MSc., of the University of Manitoba, Canada, and colleagues performed a systematic review and meta-analysis of randomized controlled trials comparing hydroxyethyl starch with other intravenous fluids (crystalloids, albumin, or gelatin) for acute fluid resuscitation in critically ill patients. The primary outcomes of interest were mortality and the incidence of acute kidney injury. Additionally, the researchers investigated the influence of the studies conducted by Boldt and colleagues on these outcomes.
After a review of the medical literature, the authors identified 38 trials that met criteria for inclusion in the analysis. Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias and strength of evidence were assessed.
The researchers found that the majority of trials were categorized as having an unclear risk or high risk of bias. For the 10,880 patients in studies contributing mortality data, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. This summary effect measure included results from seven trials performed by Boldt et al. When these seven trials that involved 590 patients were excluded, hydroxyethyl starch was found to be associated with a significantly increased risk of mortality (among 10,290 patients), renal failure (among 8,725 patients), and increased use of renal replacement therapy (among 9,258 patients).
"This study also demonstrates the importance of revising and revisiting recommendations and guidelines in light of new systematic reviews and evidence," the authors of a JAMA editorial about the study wrote.