Hydroxyethyl Starch (DB09106): A Comprehensive Monograph on a Controversial Plasma Volume Expander

Abstract

Hydroxyethyl Starch (HES) is a class of synthetic colloids, chemically derived from plant amylopectin, that was developed and widely adopted for intravascular volume expansion. Its primary indication has been the treatment and prevention of hypovolemia resulting from acute blood loss in settings such as surgery and trauma. The mechanism of action is based on the principles of colloid osmosis; the large polysaccharide molecules are retained within the vasculature, exerting oncotic pressure that draws fluid from the interstitial space to expand plasma volume. However, the clinical history of HES is dominated by a significant controversy that has reshaped fluid resuscitation practices globally. A compelling body of evidence, most notably from the landmark randomized controlled trials VISEP, 6S, and CHEST, systematically demonstrated a clear and consistent association between HES administration and severe adverse outcomes, particularly in critically ill and septic patient populations. These trials revealed an increased risk of mortality, a significantly higher incidence of acute kidney injury (AKI) necessitating renal replacement therapy (RRT), and clinically relevant coagulopathy leading to increased bleeding and transfusion requirements. These findings were not confined to older, high-molecular-weight formulations but were also demonstrated with "modern," lower-molecular-weight tetrastarches, refuting the hypothesis that newer agents were safer. The irrefutable evidence of harm prompted decisive regulatory actions, including a Black Box Warning from the U.S. Food and Drug Administration (FDA) and progressive restrictions culminating in a market suspension recommendation from the European Medicines Agency (EMA). Consequently, HES has been largely relegated from clinical practice, replaced by safer and often less expensive alternatives such as balance