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  • Letter
  • Open Access

Patient-centered outcomes and trials of hydroxyethyl starch

Critical Care201317:452

  • Published:


  • Starch
  • Renal Replacement Therapy
  • Insulin Therapy
  • Institutional Ethic Committee
  • Hydroxyethyl

Meybohm and colleagues [1] propose that hydroxyethyl starch (HES) may be used safely in hypovolemicpatients by applying a clinical algorithm and by restricting the doseadministered.

The authors question the validity of the results of the two trials that constituteover 60% of current data [2, 3] and misleadingly state that in the Crystalloid vs. Hydroxyethyl StarchTrial (CHEST), HES administration did not increase the use of renal replacementtherapy by referring to the adjusted analyses that were published in the electronicsupplement [2]. The unadjusted analysis was pre-specified as the principal outcomemeasure and is the appropriate measure to influence clinical practice. The authorsalso ignore the consistent signal of harm associated with HES, specificallyincreased mortality and use of renal replacement therapy that is evident despitewide variations in aggregate doses of HES in the three major clinical trials: 70ml/kg in the Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsistrial [4], 44 ml/kg in the Scandinavian Starch for Severe Sepsis/Septic Shock study [3], and 5 ml/kg in CHEST. Meybohm and colleagues make no comment thatadverse effects of HES represent an overall toxic effect caused by increased tissueaccumulation that is recognised as a dose-dependent, generic HES effect [5].

The ‘presumably correct indication’ and the algorithm they propose havenot been validated nor are they supported by any credible clinical evidence. Theirproposed algorithm and target population must be evaluated in rigorously conductedrandomized controlled trials before being considered for adoption into clinicalpractice. Given the consistent evidence that HES is nephrotoxic and may increasemortality [6], it is doubtful that institutional ethics committees would approve such atrial, or that informed patients would consent to participate.



Crystalloid vs. Hydroxyethyl Starch Trial


Hydroxyethyl starch.


Authors’ Affiliations

The George Institute for Global Health,, Level 13 321 Kent Street, Sydney, 2000, Australia
St George Clinical School University of New South Wales, Gray Street,Kogarah, Sydney, 2217, Australia
Royal North Shore Hospital University of Sydney,, Reserve Road, St Leonards Sydney, 2065, Australia
Austin Hospital University of Melbourne, Studley Road, Heidelberg Melbourne, 3084, Australia


  1. Meybohm P, Van Aken H, De Gasperi A, De Hert S, Della Rocca G, Girbes AR, Gombotz H, Guidet B, Hasibeder W, Hollmann MW, Ince C, Jacob M, Kranke P, Kozek-Langenecker S, Loer SA, Martin CD, Siegemund M, Wunder C, Zacharowski K: Re-evaluating currently available data and suggestions for planningrandomised controlled studies regarding the use of hydroxyethyl-starch incritically ill patients - a multidisciplinary statement. Crit Care 2013, 17: R166. 10.1186/cc12845PubMed CentralView ArticlePubMedGoogle Scholar
  2. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McgGuinness S, Rajbhandari D, Taylor CB, Webb SAR, the CHEST Investigators and the Australian and New Zealand IntensiveCare Society Clinical Trials Group: Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012, 367: 1901-1911. 10.1056/NEJMoa1209759View ArticlePubMedGoogle Scholar
  3. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Møller MH, Elkjær JM, Poulson LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quiset L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard A-L, Fabritius ML, Mondrup F, Pott FC, et al.: Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severesepsis. N Engl J Med 2012, 367: 124-134. 10.1056/NEJMoa1204242View ArticlePubMedGoogle Scholar
  4. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358: 125-139. 10.1056/NEJMoa070716View ArticlePubMedGoogle Scholar
  5. Bellmann R, Feistritzer C, Wiedermann CJ: Effect of molecular weight and substitution on tissue uptake of hydroxyethylstarch: a meta-analysis of clinical studies. Clin Pharmacokinet 2012, 51: 225-236. 10.2165/11594700-000000000-00000View ArticlePubMedGoogle Scholar
  6. Mutter TC, Ruth CA, Dart AB: Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidneyfunction. Cochrane Database Syst Rev 2013, 7:-CD007594.Google Scholar


© BioMed Central Ltd. 2013