Hydroxyethyl starch for intravenous volume replacement: more harm than benefit

Hydroxyethyl starches are synthetic fluid products used commonly in clinical practice worldwide. They received market approval in the 1960s without evaluation of their efficacy and safety. Subsequent studies reported mixed evidence on their benefits and harms. Adding to the controversy, a number of studies reporting benefit were conducted by Dr Joachim Boldt, an investigator who had a large number of studies retracted for ethical or scientific misconduct. A recent meta-analysis from Zarychanski and colleagues included 10 868 patients from 38 trials comparing hydroxyethyl starch with crystalloids, albumin or gelatin. The meta-analysis investigated the association between use of hydroxyethyl starch and renal outcomes and mortality, and generated summary estimates with and without seven studies published by Boldt et al. After exclusion of the Boldt studies, the authors found that hydroxyethyl starch was associated with a significantly increased risk of mortality (risk ratio [RR], 1.09; 95% CI, 1.02-1.17) and renal failure (RR, 1.27; 95% CI 1.09-1.47). This meta-analysis4 included 3 additional randomized trials published in 2012—the Crystalloid Versus Hydroxyethyl Starch Trials (CHEST), the Scandinavian Starch for Severe Sepsis/Septic Shock Trial (6S), and the Crystalloids Morbidity Associated With Severe Sepsis (CRYSTMAS) trial, which together accounted for 56% of the total weight of the pooled analysis. In addition to confirming the potential nephrotoxic effect associated with hydroxyethyl starch, this meta-analysis is the first to demonstrate that use of hydroxyethyl starch for acute volume replacement is also associated with a significant risk of mortality.