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Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement

Patrick Meybohm1, Hugo Van Aken2, Andrea De Gasperi3, Stefan De Hert4, Giorgio Della Rocca5, Armand RJ Girbes6, Hans Gombotz7, Bertrand Guidet8, Walter Hasibeder9, Markus W Hollmann10, Can Ince11, Matthias Jacob12, Peter Kranke13, Sibylle Kozek-Langenecker14, Stephan Alexander Loer15, Claude Martin16, Martin Siegemund17, Christian Wunder13 and Kai Zacharowski1*

Author Affiliations

1 Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

2 Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A 1, 48149 Münster, Germany

3 Dipartimento dei Trapiant, Azienda Ospedaliera 'Ospedale Niguarda Ca' Granda', Piazza dell'Ospedale Maggiore 3, 20162 Milan, Italy

4 Department of Anesthesiology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium

5 Department of Anesthesia and Intensive Care Medicine, Medical School of the University of Udine, University of Udine, via Palladio 8, 33100 Udine, Italy

6 Department of Intensive Care, University Hospital VU Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

7 Abteilung für Anästhesiologie und operative Intensivmedizin, AKh Allgemeines Krankenhaus der Stadt Linz GmbH, Krankenhausstrasse 9, 4020 Linz, Austria

8 Reanimation Medicale, Hospital Saint Antoine, 184 rue du Faubourg, Saint Antoine, 75012 Paris, France

9 Anästhesie, Intensiv- und Palliativmedizin, Krankenhaus der Barmherzigen Schwestern Ried, Schloßberg 1, 4910 Ried im Innkreis, Austria

10 Department of Anesthesiology, Academic Medical Center Amsterdam (AMC), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

11 Department of Intensive Care, Erasmus MC University Medical Centre Rotterdam, Doctor Molewaterplein 50-60, 3015 GE Rotterdam, The Netherlands

12 Klinik für Anästhesiologie, Klinikum der Universität München, Nußbaumstraße 20, 80336 München, Germany

13 Department of Anaesthesia and Critical Care, University Hospital Würzburg, Oberdürrbacher Straße 6, 97078 Würzburg, Germany

14 Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus, Hans-Sachs-Gasse 12, 1180 Vienna, Austria

15 Department of Anesthesiology, University Hospital VU Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands

16 Intensive Care and Trauma Center, Marseilles School of Medicine, Nord University Hospital, Chemin des Bourrely, 13915 Marseilles, France

17 Department of Anaesthesia, Intensive Care and Rescue Medicine, State Hospital Baden AG, Im Ergel 1, 5404 Baden, Switzerland

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Critical Care 2013, 17:R166  doi:10.1186/cc12845

Published: 26 July 2013



Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.


We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.


Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).


The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.