Old versus New Starches: What do We Know about their Differences?

  • C. Hartog
  • F. M. Brunkhorst
  • K. Reinhart


Fluid therapy is the mainstay of critical care with the goal of restoring the circulating intravascular volume, maintaining organ perfusion, and reestablishing the balance between oxygen demand and delivery. Colloids are used as plasma expanders on the grounds that these macromolecules remain in the vasculature longer than crystalloids and, therefore, increase cardiac preload with less fluid needed than crystalloids. Hydroxyethyl starches (HES) are synthetic colloids which are popular plasma expanders in Europe [1, 2, 3]. However, evidence is accumulating that HES administration has adverse effects on kidney function, coagulation, and even may increase mortality in patients with severe sepsis [4, 5, 6, 7, 8]. Critics of these studies argue that outdated HES solutions were used and that ‘new’ HES solutions are safer and can be used without concern [9, 10]. HES 130/0.4 (tetrastarch) is the latest solution, available in Europe since 2000 and recently also in the US [11]. This chapter summarizes the evidence about the safety of ‘old’ and ‘new’ HES solutions.


Severe Sepsis Hydroxyethyl Starch Cardiac Surgical Patient Major Orthopedic Surgery High Cumulative Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Schortgen F, Deye N, Brochard L (2004) Preferred plasma volume expanders for critically ill patients: results of an international survey. Intensive Care Med 30: 2222–2229CrossRefPubMedGoogle Scholar
  2. 2.
    FLUIDS study investigators for the Scandinavian Critical Care Trials Group (2008) Preferences for colloid use in Scandinavian intensive care units. Acta Anaesthesiol Scand 52: 750–758CrossRefGoogle Scholar
  3. 3.
    Basora M, Moral V, Llau JV, Silva S (2007) [Perioperative colloid administration: a survey of Spanish anesthesiologists’ attitudes]. Rev Esp Anestesiol Reanim 54: 162–168PubMedGoogle Scholar
  4. 4.
    Schortgen F, Lacherade JC, Bruneel F, et al (2001) Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 357: 911–916CrossRefPubMedGoogle Scholar
  5. 5.
    Wilkes MM, Navickis RJ, Sibbald WJ (2001) Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding. Ann Thorac Surg 72: 527–533CrossRefPubMedGoogle Scholar
  6. 6.
    Jonville-Bera AP, Autret-Leca E, Gruel Y (2001) Acquired type I von Willebrand’s disease associated with highly substituted hydroxyethyl starch. N Engl J Med 345: 622–623CrossRefPubMedGoogle Scholar
  7. 7.
    Brunkhorst FM, Engel C, Bloos F, et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358: 125–139CrossRefPubMedGoogle Scholar
  8. 8.
    Pillebout E, Nochy D, Hill G, et al (2005) Renal histopathological lesions after orthotopic liver transplantation (OLT). Am J Transplant 5: 1120–1129CrossRefPubMedGoogle Scholar
  9. 9.
    Godet G, Lehot JJ, Janvier G, Steib A, De Castro V, Coriat P (2008) Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial. Eur J Anaesthesiol 25: 986–994CrossRefPubMedGoogle Scholar
  10. 10.
    Jungheinrich C, Sauermann W, Bepperling F, Vogt NH (2004) Volume efficacy and reduced influence on measures of coagulation using hydroxyethyl starch 130/0.4 (6 %) with an optimised in vivo molecular weight in orthopaedic surgery: a randomised, double-blind study. Drugs R D 5: 1–9CrossRefPubMedGoogle Scholar
  11. 12.
    Treib J, Baron JF, Grauer MT, Strauss RG (1999) An international view of hydroxyethyl starches. Intensive Care Med 25: 258–268CrossRefPubMedGoogle Scholar
  12. 13.
    Sirtl C, Laubenthal H, Zumtobel V, Kraft D, Jurecka W (1999) Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related. Br J Anaesth 82: 510–515PubMedGoogle Scholar
  13. 14.
    Jacob M, Rehm M, Orth V, et al (2003) [Exact measurement of the volume effect of 6% hydoxyethyl starch 130/0.4 (Voluven) during acute preoperative normovolemic hemodilution]. Anaesthesist 52: 896–904CrossRefPubMedGoogle Scholar
  14. 15.
    Gallandat Huet RC, Siemons AW, Baus D, et al (2000) A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery. Can J Anaesth 47: 1207–1215CrossRefPubMedGoogle Scholar
  15. 16.
    Gandhi SD, Weiskopf RB, Jungheinrich C, et al (2007) Volume replacement therapy during major orthopedic surgery using Voluven (hydroxyethyl starch 130/0.4) or hetastarch. Anesthesiology 106: 1120–1127CrossRefPubMedGoogle Scholar
  16. 17.
    Auwerda JJ, Leebeek FW, Wilson JH, van Diggelen OP, Lam KH, Sonneveld P (2006) Acquired lysosomal storage caused by frequent plasmapheresis procedures with hydroxyethyl starch. Transfusion 46: 1705–1711CrossRefPubMedGoogle Scholar
  17. 18.
    Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P (1996) Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 348: 1620–1622CrossRefPubMedGoogle Scholar
  18. 19.
    Jungheinrich C, Scharpf R, Wargenau M, Bepperling F, Baron JF (2002) The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 mL) in mild-to-severe renal impairment. Anesth Analg 95: 544–551CrossRefPubMedGoogle Scholar
  19. 20.
    Boldt J, Brenner T, Lehmann A, Lang J, Kumle B, Werling C (2003) Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Intensive Care Med 29: 763–769PubMedGoogle Scholar
  20. 21.
    Boldt J, Scholhorn T, Mayer J, Piper S, Suttner S (2006) The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery. Anesth Analg 103: 191–199CrossRefPubMedGoogle Scholar
  21. 22.
    Boldt J, Brosch C, Ducke M, Papsdorf M, Lehmann A (2007) Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: a comparison with human albumin. Crit Care Med 35: 2740–2746CrossRefPubMedGoogle Scholar
  22. 23.
    Blasco V, Leone M, Antonini F, Geissler A, Albanese J, Martin C (2008) Comparison of the novel hydroxyethylstarch 130/0.4 and hydroxyethylstarch 200/0.6 in brain-dead donor resuscitation on renal function after transplantation. Br J Anaesth 100: 504–508CrossRefPubMedGoogle Scholar
  23. 24.
    Hussain SF, Drew PJ (1989) Acute renal failure after infusion of gelatins. BMJ 299: 1137–1138CrossRefPubMedGoogle Scholar
  24. 25.
    Levi M, Jonge E (2007) Clinical relevance of the effects of plasma expanders on coagulation. Semin Thromb Hemost 33: 810–815CrossRefPubMedGoogle Scholar
  25. 26.
    Egli GA, Zollinger A, Seifert B, Popovic D, Pasch T, Spahn DR (1997) Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation. Br J Anaesth 78: 684–689PubMedGoogle Scholar
  26. 27.
    Tseng MY, Hutchinson PJ, Kirkpatrick PJ (2008) Effects of fluid therapy following aneurysmal subarachnoid haemorrhage: a prospective clinical study. Br J Neurosurg 22: 257–268CrossRefPubMedGoogle Scholar
  27. 28.
    Haynes GR, Havidich JE, Payne KJ (2004) Why the Food and Drug Administration changed the warning label for hetastarch. Anesthesiology 101: 560–561CrossRefPubMedGoogle Scholar
  28. 29.
    Boldt J, Ducke M, Kumle B, Papsdorf M, Zurmeyer EL (2004) Influence of different volume replacement strategies on inflammation and endothelial activation in the elderly undergoing major abdominal surgery. Intensive Care Med 30: 416–422CrossRefPubMedGoogle Scholar
  29. 30.
    Kasper SM, Meinert P, Kampe S, et al (2003) 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 99: 42–47CrossRefPubMedGoogle Scholar
  30. 31.
    Langeron O, Doelberg M, Ang ET, Bonnet F, Capdevila X, Coriat P (2001) 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 92: 855–862CrossRefPubMedGoogle Scholar
  31. 32.
    Haisch G, Boldt J, Krebs C, Suttner S, Lehmann A, Isgro F (2001) Influence of a new hydroxyethylstarch preparation (HES 130/0.4) on coagulation in cardiac surgical patients. J Cardiothorac Vasc Anesth 15: 316–321CrossRefPubMedGoogle Scholar
  32. 33.
    Haisch G, Boldt J, Krebs C, Kumle B, Suttner S, Schulz A (2001) The influence of intravascular volume therapy with a new hydroxyethyl starch preparation (6 % HES 130/0.4) on coagulation in patients undergoing major abdominal surgery. Anesth Analg 92: 565–571CrossRefPubMedGoogle Scholar
  33. 34.
    Mittermayr M, Streif W, Haas T, et al (2007) Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration. Anesth Analg 105: 905–917CrossRefPubMedGoogle Scholar
  34. 35.
    Mittermayr M, Streif W, Haas T, et al (2008) Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo. Br J Anaesth 100: 307–314CrossRefPubMedGoogle Scholar
  35. 36.
    Nielsen VG (2006) Hemodilution modulates the time of onset and rate of fibrinolysis in human and rabbit plasma. J Heart Lung Transplant 25: 1344–1352CrossRefPubMedGoogle Scholar
  36. 37.
    Kozek-Langenecker SA, Jungheinrich C, Sauermann W, Van der Linden P (2008) 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 107: 382–390CrossRefPubMedGoogle Scholar
  37. 38.
    Thompson WL, Fukushima T, Rutherford RB, Walton RP (1970) Intravascular persistence, tissue storage, and excretion of hydroxyethyl starch. Surg Gynecol Obstet 131: 965–972PubMedGoogle Scholar
  38. 39.
    Stander S, Szepfalusi Z, Bohle B, et al (2001) Differential storage of hydroxyethyl starch (HES) in the skin: an immunoelectron-microscopical long-term study. Cell Tissue Res 304: 261–269CrossRefPubMedGoogle Scholar
  39. 40.
    Legendre C, Thervet E, Page B, Percheron A, Noel LH, Kreis H (1993) Hydroxyethylstarch and osmotic-nephrosis-like lesions in kidney transplantation. Lancet 342: 248–249CrossRefPubMedGoogle Scholar
  40. 41.
    Eisenbach C, Schonfeld AH, Vogt N, et al (2007) Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: influence of molecular weight and degree of substitution. Intensive Care Med 33: 1637–1644CrossRefPubMedGoogle Scholar
  41. 42.
    Leuschner J, Opitz J, Winkler A, Scharpf R, Bepperling F (2003) Tissue storage of 14Clabelled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5 after repeated intravenous administration to rats. Drugs R D 4: 331–338CrossRefPubMedGoogle Scholar
  42. 43.
    Bork K (2005) Pruritus precipitated by hydroxyethyl starch: a review. Br J Dermatol 152: 3–12CrossRefPubMedGoogle Scholar
  43. 44.
    Waitzinger J, Bepperling F, Pabst G, Opitz J (2003) Hydroxyethyl starch (HES) [130/0.4], a new HES specification: pharmacokinetics and safety after multiple infusions of 10% solution in healthy volunteers. Drugs R D 4: 149–157CrossRefPubMedGoogle Scholar
  44. 45.
    Schmidt-Hieber M, Loddenkemper C, Schwartz S, Arntz G, Thiel E, Notter M (2006) Hydrops lysosomalis generalisatus — an underestimated side effect of hydroxyethyl starch therapy? Eur J Haematol 77: 83–85CrossRefPubMedGoogle Scholar
  45. 46.
    Ginz HF, Gottschall V, Schwarzkopf G, Walter K (1998) [Excessive tissue storage of colloids in the reticuloendothelial system]. Anaesthesist 47: 330–334CrossRefPubMedGoogle Scholar
  46. 47.
    Christidis C, Mal F, Ramos J, et al (2001) Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions. J Hepatol 35: 726–732CrossRefPubMedGoogle Scholar
  47. 48.
    The Hemodilution in Stroke Study Group (1989) Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. Stroke 20: 317–323Google Scholar
  48. 49.
    Sedrakyan A, Gondek K, Paltiel D, Elefteriades JA (2003) Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Chest 123: 1853–1857CrossRefPubMedGoogle Scholar
  49. 50.
    van Rijen EA, Ward JJ, Little RA (1998) Effects of colloidal resuscitation fluids on reticuloendothelial function and resistance to infection after hemorrhage. Clin Diagn Lab Immunol 5: 543–549PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • C. Hartog
    • 1
  • F. M. Brunkhorst
    • 1
  • K. Reinhart
    • 1
  1. 1.Department of Anesthesiology and Intensive CareFriedrich-Schiller UniversityJenaGermany

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