FDA: No starch solutions for critically ill, cardiopulmonary bypass patients


The Food and Drug Administration is warning that hydroxyethyl starch solutions should no longer be used in the treatment of critically ill adult patients –including patients with sepsis and those admitted to an intensive care unit – after completing an analysis of data indicating that treatment with these solutions increases the risk of death and renal injury in these groups.

In a statement, the agency also recommended that the use of hydroxyethyl starch (HES) solutions, used as plasma volume expanders, be avoided in patients who are having open heart surgery with cardiopulmonary bypass, because of an increased risk of excessive bleeding.

The FDA is making these recommendations after completing an analysis of data from randomized controlled trials, meta-analyses, and observational studies in thousands of critically ill patients, and from a meta-analysis of 18 randomized controlled trials of almost 1,000 patients undergoing open heart surgery with cardiopulmonary bypass. The risks and benefits of HES products were the focus of a meeting in September 2012 convened by the FDA.

"Based on the totality of the evidence, [the] FDA considers increased mortality and renal injury requiring RRT [renal replacement therapy] in critically ill adult patients, including patients with sepsis and those admitted to the ICU, and excess bleeding in patients undergoing open heart surgery in association with cardiopulmonary bypass, to be HES class effects," according to the statement. The agency also recommended that health care professionals avoid the use of these products in patients with preexisting renal dysfunction, discontinue their use at the first sign of renal injury, and monitor renal function for at least 90 days in all patients. In addition, HES products should be discontinued "at the first sign of coagulopathy."

The data on critically ill adults included three double-blind, multicenter, randomized controlled studies published in 2012, which compared HES with saline solution or Ringer’s acetate, in patients with severe sepsis (two studies), or patients in the ICU who had sepsis, had undergone elective surgery, and had an APACHE II score of at least 25. In these studies, which monitored patients for 90 days, HES was associated with increased mortality and/or renal injury requiring RRT, the FDA statements said. The results of meta-analyses and observational studies in similar populations lend additional support to these findings, the statement added.

But there was no evidence of an increased risk of renal injury associated with these products in a review of 59 randomized controlled studies of adult and pediatric surgical patients who received HES in the operating room and were followed for less than a week. This could have been due to less exposure to the product, a relatively short follow-up, being relatively healthy, or some unknown factor, the statement said.

In the meta-analysis of studies of patients undergoing open heart surgery with cardiopulmonary bypass, the "use of different HES products, irrespective of molecular weight or degree of molar substitution, was associated with increased bleeding," according to the statement. The meta-analysis was published in 2012 (J. Thoracic Cardiovasc. Surg. 2012:144;223-30).

A boxed warning about the risk in ICU and septic patients is being added to the labels of HES products, and the information about the excessive bleeding risk in open heart surgery patients is being added to the warnings and precautions section.

There are four FDA-approved HES products for treating and preventing hypovolemia; they are used when plasma volume expansion is needed: HESPAN (6% HES 450/0.7a in sodium chloride injection) manufactured by B. Braun Medical); Hetastarch (6%) in 0.9% sodium chloride injection, a generic equivalent of Hespan, manufactured by Teva Pharmaceuticals USA; Hextend (6% HES 450/0.7 in physiologic solution), manufactured by BioTime; and Voluven (6% HES 130/0.4 in normal saline), manufactured by Fresenius Kabi USA.

The advisory is available at Adverse events associated with HES solutions should be reported to the FDAs MedWatch program at 80-332-1088 or

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