• Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S--Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomised clinical trial.

      Perner, Anders; Haase, Nicolai; Wetterslev, Jørn; Aneman, Anders; Tenhunen, Jyrki; Guttormsen, Anne Berit; Klemenzson, Gudmundur; Pott, Frank; Bødker, Karen Doris; Bådstøløkken, Per Martin; et al. (BioMed Central, 2011)
      BACKGROUND: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. METHODS/DESIGN: The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. DISCUSSION: The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed.
    • Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

      Perner, Anders; Haase, Nicolai; Guttormsen, Anne B; Tenhunen, Jyrki; Klemenzson, Gudmundur; Åneman, Anders; Madsen, Kristian R; Møller, Morten H; Elkjær, Jeanie M; Poulsen, Lone M; et al. (2012-07-12)
      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. 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. 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. 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.)
    • Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate.

      Perner, Anders; Haase, Nicolai; Winkel, Per; Guttormsen, Anne B; Tenhunen, Jyrki; Klemenzson, Gudmundur; Müller, Rasmus G; Aneman, Anders; Wetterslev, Jørn; Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark c Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway d Department of Clinical Medicine 1, University of Bergen, Bergen, Norway e Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland f Department of Surgical Sciences/Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden g Department of Anaesthesia and Intensive Care, Landspitali, Reykjavik, Iceland h Department of Intensive Care, Liverpool Hospital, Sydney, NSW, Australia (Springer, 2014-07)
      We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate.