title: Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis.
abstract: OBJECTIVE
  To assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis.
  
  
  METHODS
  Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
  
  
  METHODS
  Cochrane Library, Medline, Embase, Biosis Previews, Science Citation Index Expanded, CINAHL, Current Controlled Trials, Clinicaltrials.gov, and Centerwatch to September 2012; hand search of reference lists and other systematic reviews; contact with authors and relevant pharmaceutical companies.
  
  
  METHODS
  Eligible trials were randomised clinical trials comparing hydroxyethyl starch 130/0.38-0.45 with either crystalloid or human albumin in patients with sepsis. Published and unpublished trials were included irrespective of language and predefined outcomes.
  
  
  METHODS
  Two reviewers independently assessed studies for inclusion and extracted data on methods, interventions, outcomes, and risk of bias. Risk ratios and mean differences with 95% confidence intervals were estimated with fixed and random effects models.
  
  
  RESULTS
  Nine trials that randomised 3456 patients with sepsis were included. Overall, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% confidence interval 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% confidence interval 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% confidence interval -20 to 149 mL, three trials).
  
  
  CONCLUSIONS
  In conventional meta-analyses including recent trial data, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin increased the use of renal replacement therapy and transfusion with red blood cells, and resulted in more serious adverse events in patients with sepsis. It seems unlikely that hydroxyethyl starch 130/0.38-0.45 provides overall clinical benefit for patients with sepsis.
authors: Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. nicolai.haase@rh.regionh.dk
authors: Nicolai
authors: N
authors: Haase
authors: Anders
authors: A
authors: Perner
authors: Louise Inkeri
authors: LI
authors: Hennings
authors: Martin
authors: M
authors: Siegemund
authors: Bo
authors: B
authors: Lauridsen
authors: Mik
authors: M
authors: Wetterslev
authors: Jørn
authors: J
authors: Wetterslev
mesh_terms: D000077324:Crystalloid Solutions; D005440:Fluid Therapy / Q000379:methods*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007552:Isotonic Solutions / Q000627:therapeutic use*; D018805:Sepsis / Q000628:therapy*; D012709:Serum Albumin / Q000627:therapeutic use*
chemical_list: D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D012709:Serum Albumin