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Human albumin: ICU

At the moment, there are at least four different large RCTs (either completed, planned or ongoing), which aim at evaluating the possible benefit of albumin administration compared with standard crystalloid infusion in this category of patients (see Table 1). The Early Albumin Resuscitation during Septic Shock – NCT00327704 (EARSS) and the Albumin Italian Outcome Sepsis trial – NCT00707122 (ALBIOS) trials have been recently completed (although still unpublished), whereas the PRECISE

Severe sepsis or septic shock After the post hoc analysis on the pre-defined subgroup of patients with severe sepsis enrolled in the SAFE study, many investigators have focused their attention on the potential benefit of human albumin in severe sepsis or septic shock.19

patients, is a Brazilian multicentre, double-blind RCT that planned an enrolment of 360 patients with early severe sepsis, randomised to receive either 4% albumin or ringer lactate for fluid resuscitation. Thus, in the near future, novel findings will have the possibility of clarifying the potential benefits of albumin administration beyond a safe volume effect in case of hypovolaemia in patients with sepsis syndromes. Moreover, these trials, having both similarities and differences, will allow us to better dissect the effects of albumin, in terms of patient characteristics (severe sepsis versus septic shock), adequate timing of treatment (early versus late), adequate trigger for albumin administration (volume versus albumin replacement),

"Human albumin has a crucial role in regulating the homeostasis of the intravascular blood compartment"

trial has undergone only a pilot phase, pending the publication of the findings observed in the two first trial so as to decide how to proceed.20

In particular,

the EARSS trial is a French multicentre, open-label RCT that enrolled 794 patients with early septic shock randomised to receive either 20% albumin or normal saline for the first three days of fluid resuscitation, at fixed doses (100ml every eight hours). In contrast, the ALBIOS trial is an Italian multicentre, open-label RCT that planned an enrolment of 1800 patients with severe sepsis from 100 Italian ICUs. Patients have been randomised to receive either 20% albumin and crystalloids or crystalloids alone during the first phase of volume replacement and targeting, during the next 28 days, serum albumin concentration equal to or greater than 30g/l.3

Similarly to the

EARSS study, the PRECISE trial (Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock), designed as a Canadian multicentre, double-blind RCT, has planned to enrol 1800 patients with early septic shock, who will be randomised to receive either 5% albumin or normal saline as fluid challenges during volume resuscitation for a maximal period of 90 days.20

the RASP trial (Lactated Ringer versus Albumin in Early Sepsis Therapy – NCT01337934), which is now recruiting

and adequate concentration of albumin solutions (20% versus 4–5%).


There is a strong biological and physiological rationale on which it is reasonable to hypothesise a potential beneficial effect of human albumin administration in the critically ill. At the same time, the available clinical evidence is limited. A key limiting factor is the large heterogeneity characterising the population of critically ill. Therefore, a crucial next step will be to characterise the effects of albumin administration in specific categories of patient. As an example, it is now recommended that human albumin should not be employed in patients with traumatic brain injury; in contrast, patients with severe sepsis or septic shock may benefit from its use. It is very likely that the upcoming novel findings from recently concluded RCTs will better clarify this issue. l

References 1. Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology 2005;41(6):1211–9.


2. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ 1998;317(7153):235–40. 3. Vincent J-L, Navickis R, Wilkes M. Morbidity in

hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med 2004;32:2029–38.

4. Caironi P, Gattinoni L. The clinical use of albumin: the point of view of a specialist in intensive care. Blood Transfus 2009;7(4):259–67.

5. Weil MH, Henning RJ, Puri VK. Colloid oncotic pressure: clinical significance. Crit Care Med 1979;7(3):113–6.

6. King TP. On the sulfhydryl group of human plasma albumin. J Biol Chem 1961;236:C5.

7. Stamler JS et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 1992;89(16):7674–7.

8. Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res 2010;87(2):198–210.

9. Perner A et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367(2):124–34.

10. Myburgh JA et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367(20):1901–11.

11. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;2:CD000567.

12. Finfer S et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 2011;37(1):86–96.

13. Dellinger RP et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580–637.

14. Dubois MJ et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study. Crit Care Med 2006;34(10):2536–40.

15. Finfer S et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350(22):2247–56.

16. Myburgh J et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007;357(9):874–84.

17. Cooper DJ et al. Albumin resuscitation for traumatic brain injury: is intracranial hypertension the cause of increased mortality? J Neurotrauma 2013;30(7):512–18.

18. Van Aken HK et al. Fluid resuscitation in patients with traumatic brain injury: What is a SAFE approach? Curr Opin Anesthesiol 2012;25: 563–5.

19. Delany A et al. The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis. Crit Care Med 2011;39:386–91.

20. McIntyre L et al. The PRECISE RCT: evolution of an early septic shock fluid resuscitation trial. Transfus Med Rev 2012;26(4):333–41. 17

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