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Hydroxyethyl Starch 130/0.4 and Surgical Blood Loss

Section Editor(s): Saidman, LawrenceKozek-Langenecker, Sibylle A.; Jungheinrich, Cornelius MD; Sauermann, Wilhelm MD; van der Linden, Philippe MD

doi: 10.1213/ane.0b013e31818ee39d
Letters to the Editor: Letters & Announcements

Medical University of Vienna; Vienna, Austria;

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In Response:

We disagree with Hartog et al.1 that a reduction of almost one erythrocyte concentrate and correspondingly less blood loss is a marginal benefit. The difference for transfusion volume we found (137 mL)2 was larger than the difference between old HES types and albumin found by others (93 mL).3 Regarding cardiac surgery patients, one study using similar HES 130/0.4 and HES 200/0.5 volumes has already shown significant results regarding coagulation, drainage loss and allogeneic transfusion on its own.2,4 Two other studies used around 50 mL/kg HES 130/0.4 compared to 33 mL/kg HES 200/0.5 plus add on gelatin.2,5 Removing these two studies with unequal exposure or using exposure volumes as a covariate of the analyses would have shown even larger advantages for HES 130/0.4, but the decision was to include all relevant studies with maize starch and to not use infusion volumes as a covariate. Single patient data were available for all studies including the study population of Ickx et al.6,7 Sander et al.8 examined HES solutions of potato origin, which are not bioequivalent to maize starch products.9 It makes no scientific sense to express exposure volumes as percentages of legally registered maximum doses, given the similar volume effect of HES 130/0.4 and HES 200/0.5.4,10 Indeed, products with identical molar substitution (HES 200/0.5, 70/0.5) have similar plasma accumulation and influence on coagulation characteristics.11,12 However, third generation HES 130/0.4 (not yet included in older publications)3,11 has a reduced molar substitution, which is the single most important parameter leading to a reduced in vivo molecular weight, decreased plasma levels and tissue storage, and significantly reduced influence on coagulation.2,12,13 In the study of Neff et al.14 large doses of HES 130/0.4 (up to 70 mL/d over several days) were compared to much smaller doses of HES 200/0.5 plus albumin, without disadvantages regarding coagulation for HES 130/0.4 despite the grossly unequal HES doses.

The affiliation of all co-authors was already given on our original paper. HES 130/0.4 was expressively developed by industry and clinical scientists in order to address limitations of older HES products regarding renal excretion and influence on coagulation.

Regarding the Brunkhorst et al.15 trial we want to emphasize that although inclusion criterion regarding renal function was a serum creatinine ≤3.6 mg/dL, data on included patients who were actually withdrawn from study medication because they required dialysis and which volume therapy they received afterwards have not been published so far.

Our article confirms prior evidence that pharmacological differences of HES products may have important clinical consequences for our patients.16

Sibylle A. Kozek-Langenecker

Cornelius Jungheinrich, MD

Wilhelm Sauermann, MD

Philippe van der Linden, MD

Medical University of Vienna

Vienna, Austria

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1. Hartog C, Brunkhorst F, Reinhart K. Hydroxyethyl Starch 130/0.4 and Surgical Blood Loss. Anesth Analg 2009;108:672
2. Kozek-Langenecker SA, Jungheinrich C, Sauermann W, Van der Linden P. The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood products in major surgery: a pooled analysis of randomized clinical trials. Anesth Analg 2008;107:382–90
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5. Kasper SM, Meinert P, Kampe S, Görg C, Geisen C, Mehlhorn U, Diefenbach C. Large-dose hydroxyethyl starch 130/0.4 does not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with hydroxyethyl starch 200/0.5 at recommended doses. Anesthesiology 2003;99:42–7
6. Ickx BE, Rigolet M, Van der Linden PJ. Cardiovascular and metabolic response to acute normovolemic anemia. Effects of anesthesia. Anesthesiology 2000;93:1011–6
7. Ickx BE, Bepperling F, Melot C, Schulman C, Van der Linden PJ. Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolaemic haemodilution. Br J Anaesth 2003;91:196–202
8. Sander O, Reinhart K, Meier-Hellmann A. Equivalence of hydroxyethyl starch HES 130/0.4 and HES 200/0.5 for perioperative volume replacement in major gynaecological surgery. Acta Anaesthesiol Scand 2003;47:1151–8
9. Lehmann G, Marx G, Förster H. Bioequivalence comparison between hydroxyethyl starch 130/0.42/6:1 and hydroxyethyl starch 130/0.4/9:1. Drugs R D 2007;8:229–40
10. Langeron O, Doelberg M, Ang ET, Bonnet F, Capdevila X, Coriat R. Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5. Anesth Analg 2001;92:855–62
11. Hüttner I, Boldt J, Haisch G, Suttner S, Kumle B, Schulz H. Influence of different colloids on molecular markers of haemostasis and platelet function in patients undergoing major abdominal surgery. Br J Anaesth 2000;85:417–23
12. Jungheinrich C, Neff TA. Pharmacokinetics of hydroxyethyl starch. Clin Pharmacokinet 2005;44:681–99
13. Leuschner J, Opitz J, Winkler A, Scharpf R, Bepperling F. Tissue storage of 14C labeled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5 after repeated intravenous administration in rats. Drugs R D 2003;4:331–8
14. Neff TA, Doelberg M, Jungheinrich C, Sauerland A, Spahn DR, Stocker R. Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury. Anesth Analg 2003;96:1453–9
15. Brunkhorst FM, Englel 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. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358:125–39; supplementary material; comments in N Engl J Med 2008;358:2073; author reply 2074–5
16. Gandhi SD, Weiskopf RB, Jungheinrich C, Koorn R, Miller D, Shangraw RE, Prough DS, Baus D, Bepperling F, Warltier DC. Volume replacement therapy during major orthopedic surgery using Voluven® (hydroxyethyl starch 130/0.4) or hetastarch. Anesthesiology 2007;106: 1120–7
© 2009 International Anesthesia Research Society