Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

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.).

• Authors: Anders Perner, Nicolai Haase, Anne B Guttormsen, Jyrki Tenhunen, Gudmundur Klemenzson, Anders Åneman, Kristian R Madsen, Morten H Møller, Jeanie M Elkjær, Lone M Poulsen, Asger Bendtsen, Robert Winding, Morten Steensen, Pawel Berezowicz, Peter Søe-Jensen, Morten Bestle, Kristian Strand, Jørgen Wiis, Jonathan O White, Klaus J Thornberg, Lars Quist, Jonas Nielsen, Lasse H Andersen, Lars B Holst, Katrin Thormar, Anne-Lene Kjældgaard, Maria L Fabritius, Frederik Mondrup, Frank C Pott, Thea P Møller, Per Winkel, Jørn Wetterslev, 6S Trial Group, Scandinavian Critical Care Trials Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 367 Issue 2 Pg. 124-34 (Jul 12 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22738085 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxyethyl Starch Derivatives
• Isotonic Solutions
• Ringer's acetate

Topics

• Aged
• Double-Blind Method
• Female
• Fluid Therapy (adverse effects, methods)
• Hemorrhage (chemically induced)
• Humans
• Hydroxyethyl Starch Derivatives (adverse effects, therapeutic use)
• Intention to Treat Analysis
• Isotonic Solutions (adverse effects, therapeutic use)
• Kidney Failure, Chronic (etiology, therapy)
• Male
• Middle Aged
• Renal Replacement Therapy
• Sepsis (complications, mortality, therapy)