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In Response

Hartog, Christiane S.; Reinhart, Konrad

doi: 10.1213/ANE.0b013e31821ebdee
Letters to the Editor: Letters & Announcements

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena Germany (Hartog, Reinhart)

We appreciate Drs. Rice and Gravenstein's1 concern regarding the number of questionably valid Boldt papers included in our recent systematic analysis of randomized controlled trials (RCTs) with hydroxyethyl starch (HES) 130/0.4.2 The disclosure of a fraudulent RCT of Dr. Boldt coincided with the publication of the systematic review which included a total of 18 RCTs published by Boldt. In an accompanying editorial3 we explained that if all the Boldt studies were withdrawn from the systematic analysis the conclusion would still remain the same: “The remaining 28 surgical RCTs still have low power (median patient n=27 in HES vs. n=33 in control groups), a median study period of 18 hours, two-thirds use other starches or gelatins as control fluids and a median HES dose well below the daily dose limit…published clinical data is insufficient to allow conclusion about whether HES 130/0.4 is safer than other HES solutions in surgical and critically ill patients.”

We would also strongly encourage authors who want to keep up with science that is “without a shadow of doubt” to turn to summaries from independent groups such as the Cochrane Collaboration ( In this case, three Cochrane Reviews on HES46 concluded that HES is not superior to crystalloids or other colloids, may be harmful to the kidneys in patients at increased risk for renal failure, and that there are insufficient clinical data to support suggestions that HES 130/0.4 may be safer.

Christiane S. Hartog

Konrad Reinhart Department of Anesthesiology and Intensive Care Medicine, Jena

University Hospital, Friedrich-Schiller-University, Jena Germany

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1. Gravenstein N, Rice MJ. A bit confused. Anesth Analg 2011; 112: 1509
2. Hartog CS, Kohl M, Reinhart K. A Systematic Review of Third-Generation Hydroxyethyl Starch (HES 130/0.4) in Resuscitation: Safety Not Adequately Addressed. Anesth Analg 2011; 112: 635–45
3. Reinhart K, Takala J. Hydroxyethyl Starches: What Do We Still Know? Anesth Analg 2011; 112: 507–11
4. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2009: CD000567
5. Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation. Cochrane Database Syst Rev 2008: CD001319
6. Dart AB, Mutter TC, Ruth CA, Taback SP. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev 2010: CD007594
© 2011 International Anesthesia Research Society