2012•New England Journal of MedicineRequires access
Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis
Anders Perner, Nicolai Haase, Anne Berit Guttormsen, Jyrki J. Tenhunen, Gudmundur Klemenzson, Anders Åneman, Kristian Rørbæk Madsen, Morten Hylander Møller, Jeanie M. Elkjær, Lone Musaeus Poulsen, Asger Bendtsen, Robert Winding, Morten Steensen, Pawel Berezowicz, Peter Søe‐Jensen, Morten Heiberg Bestle, Kristian Strand, Jørgen Wiis, Jonathan O. White, Klaus Thornberg, Lars Quist, Jonas Nielsen, Lasse H. Andersen, Lars Broksø Holst, Katrín Þormar, Anne Lene Kjældgaard, Maria Louise Fabritius, Frederik Mondrup, Frank Christian Pott, Thea Palsgaard Møller, Per Winkel, Jørn Wetterslev
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Abstract
BACKGROUND: Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS: In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS: Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).