Purpose

FDA has analyzed recent data that indicate an increased risk of (i) mortality and renal injury requiring renal replacement therapy in critically ill adult patients, including patients with sepsis and those admitted to the ICU; and (ii) excess bleeding particularly in patients undergoing open heart surgery in association with cardiopulmonary bypass. Additional caution regarding the use of these products is warranted.

Summary of Safety Issues

Hydroxyethyl starch (HES) solutions are used for the treatment of hypovolemia (low blood volume) when plasma volume expansion is desired. Recent data have associated the use of these products with an increased risk of severe adverse events when used in certain patient populations.

On September 6-7, 2012, FDA convened a Public Workshop1 in collaboration with the National Heart, Lung, and Blood Institute at the National Institutes of Health, the U.S. Army Materiel Command, Department of Defense, and the Office of the Assistant Secretary of Health, Health and Human Services to discuss the risks and benefits of HES solutions. Panelists presented data from randomized controlled trials (RCTs), meta-analyses and observational studies (described in data summary) that showed increased mortality and/or renal injury requiring renal replacement therapy (RRT), i.e, severe renal injury, when HES was used in critically ill adult patients including patients with sepsis and those admitted to intensive care unit (ICU).

FDA has completed the analysis of data from the RCTs, meta-analyses and observational studies indicating increased mortality and renal injury requiring RRT in critically ill adult patients, including patients with sepsis and those admitted to the ICU who are treated with HES solutions. FDA has concluded that HES solutions should not be used in these patient populations, and a Boxed Warning to include the risk of mortality and severe renal injury is warranted. In addition, FDA has reviewed a meta-analysis of studies conducted in patients undergoing open heart surgery in association with cardiopulmonary bypass and has determined that an additional warning about excessive bleeding is needed in the Warnings and Precautions Section of the package insert.

Recommendations for Patients

Patients should be aware of the risks associated with the use of HES solutions and discuss these risks with their healthcare provider

  • Be aware that severe kidney damage has been associated with the use of HES solutions.
  • Be sure to follow up with your healthcare provider as requested and follow all instructions. Report any unusual symptoms immediately.
  • Symptoms of kidney damage can include:
    • change in the frequency, amount, or color of urine
    • blood in the urine
    • difficulty urinating
    • swelling of the legs, ankles, feet, face, or hands
    • unusual weakness or fatigue
    • nausea and vomiting
    • shortness of breath