Should Albumin be the Colloid of Choice for Fluid Resuscitation in Hypovolemic Patients?

  • J. Montomoli
  • A. Donati
  • C. InceEmail author
Part of the Annual Update in Intensive Care and Emergency Medicine book series (AUICEM)


Hemodynamic management represents a major therapeutic challenge in critical care and emergency medicine. It plays a key role during the entire healing process of a patient from hospital admission to discharge. Within hemodynamic stabilization, resuscitation is one of the major indications for fluid administration and is often a life-saving therapy that has to be administered as soon as possible, with the right dose and rate, and choosing the right types of fluid. Unfortunately, these pillars of fluid therapy are not supported by consistent and solid evidence in the scientific literature. The agreement on the right fluid for the right patient is a mantra that is still a source of debate. However, after the restriction of hydroxyethyl starch (HES) use in critically ill patients issued by the European Medicine Agency (EMA) and the Food and drug Administration (FDA) in 2013, crystalloids now dominate resuscitation fluids in hypovolemia although recent evidence has demonstrated increased mortality in critically ill patients receiving 0.9% NaCl (normal saline)—by far, one of the most used crystalloids [1].


  1. 1.
    Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829–39.CrossRefGoogle Scholar
  2. 2.
    Vincent JL, De Backer D, Wiedermann CJ. Fluid management in sepsis: the potential beneficial effects of albumin. J Crit Care. 2016;35:161–7.CrossRefGoogle Scholar
  3. 3.
    Fanali G, di Masi A, Trezza V, et al. Human serum albumin: from bench to bedside. Mol Asp Med. 2012;33:209–90.CrossRefGoogle Scholar
  4. 4.
    Kendrick DB. The blood program. 1962. Available at: Accessed 15 Aug 2018.
  5. 5.
    Caraceni P, Domenicali M, Tovoli A, et al. Clinical indications for the albumin use: still a controversial issue. Eur J Intern Med. 2013;24:721–8.CrossRefGoogle Scholar
  6. 6.
    Vincent JL, Ince C, Bakker J. Clinical review: circulatory shock—an update: a tribute to Professor Max Harry Weil. Crit Care. 2012;16:239.Google Scholar
  7. 7.
    Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40:1795–815.CrossRefGoogle Scholar
  8. 8.
    Ince C. The rationale for microcirculatory guided fluid therapy. Curr Opin Crit Care. 2014;20:301–8.CrossRefGoogle Scholar
  9. 9.
    Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care Lond Engl. 2015;19(Suppl 3):S8.Google Scholar
  10. 10.
    Weil MH. The “VIP” approach to the bedside management of shock. JAMA. 1969;207:337.CrossRefGoogle Scholar
  11. 11.
    Malbrain MLNG, Van Regenmortel N, Saugel B, et al. Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy. Ann Intensive Care. 2018;8:66.CrossRefGoogle Scholar
  12. 12.
    Dubin A, Pozo MO, Casabella CA, et al. Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. J Crit Care. 2010;25:659.e1–8.CrossRefGoogle Scholar
  13. 13.
    Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012;108:384–94.CrossRefGoogle Scholar
  14. 14.
    Kremer H, Baron-Menguy C, Tesse A, et al. Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: concentration-dependent properties. Crit Care Med. 2011;39:1414–22.CrossRefGoogle Scholar
  15. 15.
    Damiani E, Ince C, Orlando F, et al. Effects of the infusion of 4% or 20% human serum albumin on the skeletal muscle microcirculation in endotoxemic rats. PLoS One. 2016;11:e0151005.CrossRefGoogle Scholar
  16. 16.
    Hahn RG. Adverse effects of crystalloid and colloid fluids. Anaesthesiol Intensive Ther. 2014;49:303–8.Google Scholar
  17. 17.
    Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;367:124–34.CrossRefGoogle Scholar
  18. 18.
    Wise J. Boldt: the great pretender. BMJ. 2013;346:f1738.CrossRefGoogle Scholar
  19. 19.
    Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ. 1998;317:235–40.CrossRefGoogle Scholar
  20. 20.
    Roberts I, Edwards P, McLelland B, et al. More on albumin. BMJ. 1999;318:1214.CrossRefGoogle Scholar
  21. 21.
    Wilkes MM, Navickis RJ. Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials. Ann Intern Med. 2001;135:149–64.CrossRefGoogle Scholar
  22. 22.
    Vincent JL, Wilkes MM, Navickis RJ. Safety of human albumin—serious adverse events reported worldwide in 1998–2000. Br J Anaesth. 2003;91:625–30.CrossRefGoogle Scholar
  23. 23.
    Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247–56.CrossRefGoogle Scholar
  24. 24.
    Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.CrossRefGoogle Scholar
  25. 25.
    Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367:1901–11.CrossRefGoogle Scholar
  26. 26.
    James MFM, Michell WL, Joubert IA, et al. Resuscitation with hydroxyethyl starch improves renal function and lactate clearance in penetrating trauma in a randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe Trauma). Br J Anaesth. 2011;107:693–702.CrossRefGoogle Scholar
  27. 27.
    Guidet B, Martinet O, Boulain T, et al. Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study. Crit Care Lond Engl. 2012;16:R94.CrossRefGoogle Scholar
  28. 28.
    Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310:1809–17.CrossRefGoogle Scholar
  29. 29.
    Can I, Thomas WLS. Even normal saline is harmful if used wrongly, so why did EMA single out hydroxyethyl starch? 2018. Available at: Accessed 6 June 2018.
  30. 30.
    Wiedermann CJ, Bellomo R, Perner A. Is the literature inconclusive about the harm from HES? No. Intensive Care Med. 2017;43:1523–5.CrossRefGoogle Scholar
  31. 31.
    Doshi P. EMA recommendation on hydroxyethyl starch solutions obscured controversy. BMJ. 2018;360:k1287.CrossRefGoogle Scholar
  32. 32.
    Hammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: an international cross-sectional study. PLoS One. 2017;12:e0176292.CrossRefGoogle Scholar
  33. 33.
    Zwissler B. Open letter to the European Commission: marketing authorization of colloid solutions containing hydroxyethyl starch (HES). 2018. Available at: Accessed 3 Nov 2018.
  34. 34.
    Angeli P, Bernardi M, Villanueva C, et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60.CrossRefGoogle Scholar
  35. 35.
    Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet. 2018;391:2417–29.CrossRefGoogle Scholar
  36. 36.
    Solà E, Solé C, Simón-Talero M, et al. Midodrine and albumin for prevention of complications of cirrhosis in patients in the waiting list for liver transplantation. A randomized, multicenter, double-blind, placebo-controlled trial. J Hepatol. 2017;66:S11.CrossRefGoogle Scholar
  37. 37.
    Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock. Crit Care Med. 2017;45:486–552.CrossRefGoogle Scholar
  38. 38.
    Roberts I, Blackhall K, Alderson P, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2011;2011:CD001208.Google Scholar
  39. 39.
    Laki B, Taghizadeh-Ghehi M, Assarian M, et al. Effect of hospital-wide interventions to optimize albumin use in a tertiary hospital. J Clin Pharm Ther. 2017;42:704–9.CrossRefGoogle Scholar
  40. 40.
    Tarin R, Sanchez A, Santos R, et al. Costs related to inappropriate use of albumin in Spain. Ann Pharmacother. 2000;34:1198–205.CrossRefGoogle Scholar
  41. 41.
    Dubois M-J, Orellana-Jimenez C, Melot C, et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study. Crit Care Med. 2006;34:2536–40.CrossRefGoogle Scholar
  42. 42.
    Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412–21.CrossRefGoogle Scholar
  43. 43.
    Frenette AJ, Bouchard J, Bernier P, et al. Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis. Crit Care. 2014;18:602.CrossRefGoogle Scholar
  44. 44.
    Taguchi K, Giam Chuang VT, Maruyama T, Otagiri M. Pharmaceutical aspects of the recombinant human serum albumin dimer: structural characteristics, biological properties, and medical applications. J Pharm Sci. 2012;101:3033–46.CrossRefGoogle Scholar
  45. 45.
    Woodcock J, Griffin J, Behrman R, et al. The FDA’s assessment of follow-on protein products: a historical perspective. Nat Rev Drug Discov. 2007;6:437–42.CrossRefGoogle Scholar
  46. 46.
    Che Y, Wilson FJ, Bertolini J, et al. Impact of manufacturing improvements on clinical safety of albumin: Australian pharmacovigilance data for 1988–2005. Crit Care Resusc. 2006;8:334–8.PubMedGoogle Scholar
  47. 47.
    Lai AT, Zeller MP, Millen T, et al. Chloride and other electrolyte concentrations in commonly available 5% albumin products. Crit Care Med. 2018;46:e326–9.CrossRefGoogle Scholar
  48. 48.
    Bar-Or D, Bar-Or R, Rael LT, et al. Heterogeneity and oxidation status of commercial human albumin preparations in clinical use. Crit Care Med. 2005;33:1638–41.CrossRefGoogle Scholar
  49. 49.
    Plantier J-L, Duretz V, Devos V, et al. Comparison of antioxidant properties of different therapeutic albumin preparations. Biologicals. 2016;44:226–33.CrossRefGoogle Scholar
  50. 50.
    Bar-Or D, Thomas GW, Bar-Or R, et al. Commercial human albumin preparations for clinical use are immunosuppressive in vitro. Crit Care Med. 2006;34:1707–12.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Anesthesia and Intensive Care, Department of Biomedical Sciences and Public HealthUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Department of Intensive Care, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands

Personalised recommendations