Question 5

Critically evaluate the role of albumin containing solutions in the management of the critically ill patient.

[Click here to toggle visibility of the answers]

College Answer

The role of albumin containing solutions in the critically ill is becoming clearer with time, but is still controversial. Earlier meta-analyses of heterogeneous trials had suggested increased mortality with albumin administration. The recently published SAFE study confirmed that 4% albumin administration was “safe” when compared with normal saline in those critically ill patients who required fluid resuscitation, but did not suggest any specificindications. The specific predetermined and stratified subset of patients where there is still significant doubt is in patients with multiple trauma where there seemed to be worse outcomes in the albumin group (in a post-hoc analysis thought mainly in those patients with severe head injury). Two prospective RCTs have demonstrated specific situations where albumin may actually be of benefit: improved oxygenation in hypo-proteinemic patients with acute lung injury (Martin CCM 2002), and improved mortality in patients with spontaneous bacterial peritonitis (Sort NEJM1999).


This question closely resembles Question 25 from the first paper of 2010.

The answer to it is reporduced below, to simplify revision

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.