Correspondence  |   July 2015
High-molecular Hydroxyethyl Starch: Is More Data Still Needed?
Author Notes
  • University of Muenster, Muenster, Germany (H.V.A.).
  • (Accepted for publication February 25, 2015.)
    (Accepted for publication February 25, 2015.)×
Article Information
Correspondence   |   July 2015
High-molecular Hydroxyethyl Starch: Is More Data Still Needed?
Anesthesiology 7 2015, Vol.123, 234-235. doi:
Anesthesiology 7 2015, Vol.123, 234-235. doi:
To the Editor:
With some degree of amazement, we read the article by Kashy et al.1  on the influence of 6% hydroxyethyl starch (HES) 670/0.75 (Hextend; Hospira Inc., USA) on perioperative acute kidney injury in patients undergoing noncardiac surgery. The data are derived from a database of more than 120,000 patients treated in Cleveland hospitals, in which 6% HES 670/0.75 was the most commonly used colloid between 2005 and 2012. After propensity-matched multivariable analysis, the authors found a higher risk of developing more severe acute kidney injury with the use of 6% HES 670/0.75 as compared with sole crystalloids. Notably, a higher rate of acute kidney injury had already been shown with the use of high-molecular HES (6% HES 200/0.62) in critically ill patients with sepsis as compared with gelatin in 2001.2  Moreover, direct comparison of low-molecular (6% HES 130/0.4) versus high-molecular HES (10% HES 200/0.5) has shown relevant differences on renal function and integrity in the preclinical setting.3  The safety of 6% HES 130/0.4 with regard to renal function in the perioperative setting was confirmed by clinical studies and a recent meta-analysis.4,5  As a result, one pharmaceutical company has stopped the production of high-molecular HES in 2013 (Fresenius Kabi Germany). Moreover, in our department, the use of starches other than 6% HES 130/0.4 was already abandoned in 2001 for the above-mentioned reasons. It is therefore surprising that in the present database of Cleveland hospitals, more than 50% of the analyzed patients were treated with high-molecular HES despite the fact that low-molecular preparations have been available since 1999. With respect to this, the clinical relevance of the present study appears to be limited. Finally, the title of the article does not specify the type of starch that was analyzed and is therefore misleading. This is especially true because several recent publications in Anesthesiology highlighted the important differences between HES preparations.4,6 
With regard to the quality of the propensity-matched analysis, many variables that may serve as potential confounders were numerically higher in the colloid group, even though the predefined level of absolute standard difference was not exceeded. These include intraoperative fluid amounts, intraoperative hypotension, intraoperative blood loss, duration of surgery, blood transfusion, and vasopressor use, which were all higher in the matched colloid as compared with the crystalloid group. It therefore appears that the colloid group was a priori at a higher risk of developing acute kidney injury as compared with the crystalloid group. Such intrinsic differences in patient characteristics may hardly be compensated by sophisticated statistical analysis. Finally, despite the known fundamental differences between the various HES preparations,6  high-molecular HES and waxy maize-derived and potato-derived tetrastarches are not adequately differentiated in the Discussion section.
In summary, the present article investigates a fluid that is known to be unsuitable for modern perioperative care, despite starches with a better renal safety profile are available for perioperative use. Relevant baseline differences may limit valid conclusions from the present dataset.
Competing Interests
The authors declare no competing interests.
Christian Ertmer, M.D., Hugo Van Aken, M.D., F.R.C.A., F.A.N.Z.C.A. University of Muenster, Muenster, Germany (H.V.A.).
Kashy, BK, Podolyak, A, Makarova, N, Dalton, JE, Sessler, DI, Kurz, A Effect of hydroxyethyl starch on postoperative kidney function in patients having noncardiac surgery.. Anesthesiology. (2014). 121 730–9 [Article] [PubMed]
Schortgen, F, Lacherade, JC, Bruneel, F, Cattaneo, I, Hemery, F, Lemaire, F, Brochard, L Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: A multicentre randomised study.. Lancet. (2001). 357 911–6 [Article] [PubMed]
Ertmer, C, Köhler, G, Rehberg, S, Morelli, A, Lange, M, Ellger, B, Pinto, BB, Rübig, E, Erren, M, Fischer, LG, Van Aken, H, Westphal, M Renal effects of saline-based 10% pentastarch versus 6% tetrastarch infusion in ovine endotoxemic shock.. Anesthesiology. (2010). 112 936–47 [Article] [PubMed]
Martin, C, Jacob, M, Vicaut, E, Guidet, B, Van Aken, H, Kurz, A Effect of waxy maize-derived hydroxyethyl starch 130/0.4 on renal function in surgical patients.. Anesthesiology. (2013). 118 387–94 [Article] [PubMed]
Van Der Linden, P, James, M, Mythen, M, Weiskopf, RB Review article: Safety of modern starches used during surgery.. Anesth Analg. (2013). 116 35–48 [Article] [PubMed]
Westphal, M, James, MF, Kozek-Langenecker, S, Stocker, R, Guidet, B, Van Aken, H Hydroxyethyl starches: Different products–different effects.. Anesthesiology. (2009). 111 187–202 [Article] [PubMed]