In an analysis of studies that examined critically ill patients requiring an increase in blood fluid volume, intravenous use of hydroxyethyl starch, compared with other resuscitation solutions, was not associated with decreased mortality.
Moreover, after exclusion of seven trials performed by an investigator whose research has been retracted because of scientific misconduct, the analysis of the remaining studies indicated that hydroxyethyl starch was associated with a significantly increased risk of death and acute kidney injury, researchers reported in the Feb. 20 issue of the Journal of the American Medical Association.
“Fluids are a core element in the resuscitation of critically ill patients, and the relative superiority and safety of different resuscitation solutions has been the focus of considerable debate,” the researchers wrote in background information for the study. “Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are conflicting.”
The researchers noted that in 2011, 86% of the research published by Joachim Boldt, MD, since 1999 was retracted after a government investigation reported research misconduct reflecting failure to acquire ethical approval for research and fabrication of study data. “The effect of these retractions has been far-reaching,” they 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 in 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 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 and colleagues. When these seven trials involving 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).
“Clinical use of hydroxyethyl start for acute volume resuscitation is not warranted due to serious safety concerns,” the authors concluded.
In an accompanying editorial, Massimo Antonelli, MD, and Claudio Sandroni, MD, of the Universita Cattolica del Sacro Cuore in Rome, wrote that the study “demonstrates the importance of revising and revisiting recommendations and guidelines in light of new systematic reviews and evidence.”
The study abstract is available at http://jama.jamanetwork.com/article.aspx?articleid=1653505.