Question 25

Critically evaluate the use of albumin-containing solutions in critically ill patients.

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College Answer

Albumin solutions are frequently used in critically ill patients for a variety of indications.

a) Volume replacement:  The SAFE study showed that using colloids was equivalent in efficacy and safety to crystalloids.

b) Hypoalbuminaemia: Clinical conditions that may benefit from albumin replacement for hypoalbuminaemia include:-

Patients with decompensated liver cirrhosis and spontaneous bacterial peritonitis. The administration of albumin results in a reduced incidence of renal failure and reduction in mortality.

Patients with Acute Lung Injury or ARDS.The study by Martin CCM 2005 shows that in patients who are hypoproteinaemic with ARDS, adding albumin to frusemide resulted in a significant improvement in oxygenation compared to frusemide alone. There was also a greater net negative fluid balance achieved and better haemodynamic stability in patients receiving albumin.

Head  injury:  The  clinical  conditions  in which  you  would  avoid  Albumin  replacement  is cerebral trauma where the SAFE subgroup  analysis reported increased  mortality at 28 days and 2 years.

Sepsis:  In the SAFE subgroup, a trend towards an improved outcome with albumin was noted as compared to saline

In Australia, albumin is cheap (free). It is also risk free, not associated with serious complications  such  as  coagulation  abnormalities  and  renal  failure  as  seen  with  other studies


This question is a broad "what uses for albumin can you think of" sort of question. A couple of albumin enthusiasts (Caironi and Gattinoni) have published a good overview of this topic.

Firstly, to the most notable and obvious part.

Albumin as a resuscitation fluid

  • Equivalent to saline in terms of mortality (SAFE study)

Albumin for resuscitation of septic shock

  • Slightly superior to saline in terms of mortality (on post-hoc subgroup analysis of the SAFE study)
  • Equivalent to saline in terms of mortality (ALBIOS trial)
  • Improves mortality of septic shock patients once hemodynamic stability has been achieved (also the ALBIOS trial).
  • According to a recent meta-analysis, the results of the available studies support safety, but suggest that albumin is "not robustly effective at reducing all-cause mortality".

Albumin for spontaneous bacterial peritonitis

Albumin for volume replacement in paracentesis

Albumin as an adjunct in hepatorenal syndrome

Albumin for extracorporeal detoxification in liver failure

Albumin as an adjunct to frusemide in ARDS

  • Albumin and frusemide together improve oxygenation in hypoproteinaemic ARDS patients
  • There is no mortality benefit, and robust evidence is lacking.

Albumin to aid water elimination in oedematous ICU patients

  • This practice is based on physiological principles, using albumin as an oncotic agent to attract water into the intravascular space to improve diuresis.
  • Proponents of this strategy admit that their recommendations "appear in open contrast with what is called “evidence-based medicine”".

Albumin is to be avoided in traumatic brain injury

  • Again from the SAFE study, in the same way as a post-hoc subgroup analysis revealed some benefit from albumin in sepsis, so did a similar subgroup analysis reveal some evidence of harm in patients with traumatic brain injury.

Much has been made of the findings of the SAFE study. The most recent ALBIOS study has supported the notion that albumin and saline are quivalent as resuscitation fluids. Furthermore, the authors found that the patients enrolled in early stages of sepsis did not demonstrate an early benefit, and that patients treated with albumin for longer tended to benefit more. This suggests that the benefit of albumin is derived not from a purely oncotic effect, but rather due to its ancillary functions as a nitric oxide modulator, antioxidant and anti-immunosuppressive. This is supported by the last salvo fired by Marik, who suggested that the contribution of albumin infusion to maintaining the integrity of the vascular endothelial glycocalyx is enough to support its role as "a reasonable intervention" in sepsis.


McEvoy, Rinaldo Bellomo, et al. "The SAFE Study Investigators Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis." Intensive Care Med 37 (2011): 86-96.


Finfer, Simon, et al. "A comparison of albumin and saline for fluid resuscitation in the intensive care unit." N Engl j Med 350.22 (2004): 2247-2256.


Caironi, Pietro, et al. "Albumin replacement in patients with severe sepsis or septic shock." New England Journal of Medicine 370.15 (2014): 1412-1421.


Marik, Paul E. "Early Management of Severe Sepsis: Concepts and Controversies." CHEST Journal 145.6 (2014): 1407-1418.


Patel, Amit, et al. "Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality." BMJ 349 (2014): g4561.


Myburgh, John, et al. "Saline or albumin for fluid resuscitation in patients with traumatic brain injury." N Engl J Med 357.9 (2007): 874-884.


Bernardi, Mauro, Caterina Maggioli, and Giacomo Zaccherini. "Human albumin in the management of complications of liver cirrhosis." Crit Care 16.2 (2012): 211.


Gluud, Lise L., et al. "Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome." Hepatology 51.2 (2010): 576-584.


Sort, Pau, et al. "Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis." New England Journal of Medicine 341.6 (1999): 403-409.


Karvellas, Constantine J., et al. "Bench-to-bedside review: current evidence for extracorporeal albumin dialysis systems in liver failure." Crit Care 11.3 (2007): 215.


Martin, Greg S., et al. "A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury." Critical care medicine 33.8 (2005): 1681-1687.


Caironi, Pietro, and Luciano Gattinoni. "The clinical use of albumin: the point of view of a specialist in intensive care." Blood Transfusion 7.4 (2009): 259.