Albumin Use in Critical Illness

A 70-year-old woman was admitted to the surgical ward with abdominal pain. CT scans showed some dilated loops of small bowel. She remained on the surgical ward for 5 days with minimal resolution of her symptoms. She was taken to theatre for exploratory laparotomy where she was diagnosed with faecal peritonitis from a perforated diverticulum. She had a washout and a Hartmanns procedure was performed.
She became unstable during her laparotomy requiring vasopressors and was taken to the intensive care unit postoperatively.  She was left with a laparostomy with a VAC dressing applied. She was treated with lung protective ventilation and remained cardiovascularly unstable. Two days later she was taken back to theatre for a further washout and closure of her abdomen. She developed an ileus and was then started on total parenteral nutrition. An oesophageal doppler monitor was placed to help guide her fluid status. She was extubated on day 4 post op but her filling status remained a problem to gauge. Her fluid balance became very positive and she became very oedematous. Her albumin level dropped significantly. It was then decided to give her daily intravenous albumin.
What evidence is there for the use of albumin in critically ill patients?

James Day
Human serum albumin is a single peptide chain of 585 amino acids. It has a molecular weight of 66 kDa. It has a plasma concentration of 4g/dl and represents about 60% of the total protein present in the plasma. It has many important effects. It acts as a regulator of osmotic pressure, carrier of poorly water soluble molecules and has anti-oxidant properties. Albumin is synthesized in the liver at a rate of 12-20g per day. After synthesis albumin is distributed into the intravascular and extravascular compartments. Albumin is not stored to any extent. It has a half-life of 18-20 days.
In critically ill patients the homeostasis of albumin is altered. Synthesis is decreased due to malnutrition and liver dysfunction. There is also reprioritization of protein synthesis in favour of acute reactant proteins. There is increased loss and degradation of albumin and a change in the distribution between the intravascular and extravascular space. As a result critically ill patients are frequently hypoalbuminaemic.
Low albumin levels are associated with increased complications and worse prognosis in many populations (dialysis, heart failure, cancer surgery, head trauma, upper GI bleeds). Low albumin levels on hospital discharge are also associated with worse outcomes. This has been shown to be independent of patient’s nutritional status and inflammatory status. The correlation between low albumin levels and outcome is clear. The question is whether low albumin levels cause the poor outcomes or is simply a marker of a serious disease state.
Albumin administration has been used for over 60 years. They are derived from pooled human plasma and there is a risk of viral transmission. They can also cause problems with blood typing and cause allergic reactions. In 1998 a Cochrane review performed a meta-analysis, which showed a relative risk of death of 1.67 in patients receiving albumin solutions compared with non- albumin recipients (1). The SAFE study in 2004 demonstrated the safety of albumin in critically ill patients. It was not designed though to demonstrate a beneficial effect (2).
A meta-analysis of 9 prospective controlled trials suggested complication rates could be reduced when serum albumin concentrations following albumin administration exceeded 30g/l (3). From the SAFE study patients with low serum albumin who received albumin tended to have a lower mortality than those who received saline (23.7% vs 35.3%, RR 0.87, 0.74-1.02) (4). The SAFE study also showed a non-significant trend towards greater survival in hypoalbuminaemic septic patients treated with albumin (5).
A pilot study was performed in 100 hypoalbuminaemic patients to receive either albumin (to keep levels >30g/dl) or no albumin. They reported that organ function improved more in the albumin treated group (6). They also had less positive fluid balances and greater tolerance to enteral feeding. This is been repeated in a mutli-centre study (ALBIOS trial) whose results are soon to be reported.
Albumin use has been investigated in other patient groups. There is a survival benefit to administering albumin in patients with cirrhosis with spontaneous bacterial peritonitis in addition to antibiotics (7). Martin et al. showed that the albumin together with frusemide improved oxygenation and haemodynamic stability in patients with acute lung injury or acute respiratory distress syndrome (8). However, the SAFE study showed increased mortality in patients with traumatic brain injury treated with albumin compared to those treated with saline (9).


Lessons Learnt

With the recent studies showing harm due to administration of other colloids there has been a natural interest in the extended use of albumin as a colloid. The safety issue of using albumin seems to have been resolved (with the exception of traumatic brain injury). Their use early on in acute illness seems questionable. However they may confer benefit in hypoalbuminaemic patients at risk of complications. The results of ongoing studies will hopefully offer further guidance. Future studies should aim to look at long-term follow-up, as there is always a risk when administering blood products. Health economics analysis should also be included as there are high costs associated with the use of albumin.



  1. Cochrane Injuries Group. Human albumin administration in critically ill patients: systematic review of randomized controlled trials. BMJ (Clinical Research Ed.) 1998; 317: 235–240.
  2. FinferS,BellomoR,BoyceNetal.Acomparisonofalbuminandsaline for fluid resuscitation in the intensive care unit. The New England Journal of Medicine 2004; 350: 2247–2256.
  3. VincentJL,DuboisMJ,NavickisRJ&WilkesMM.Hypoalbuminemiain acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Annals of Surgery 2003; 237: 319– 334.
  4. Finfer S, Bellomo R, McEvoy M et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the Saline versus Albumin Fluid Evaluation (SAFE) Study. BMJ (Clinical Research Ed.) 2006; 333: 1044.
  5. Vincent JL. Resuscitation using albumin in critically ill patients: research in patients at high risk of complications is now needed. BMJ (Clinical Research Ed.) 2006; 333: 1029–1030.
  6. Dubois MJ, Orellana-Jimenez C, Melot C et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study. Critical Care Medicine 2006; 34: 2536–2540.
  7. Sort P, Navasa M, Arroyo V et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. The New England Journal of Medicine 1999; 341: 403–409.
  1. Martin GS, Moss M, Wheeler AP et al. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Critical Care Medicine 2005; 33: 1681–1687.
  2. MyburghJ, CooperJ, Finfer S et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. The New England Journal of Medicine 2007; 357: 874–884.



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