Table 1 Key points in the albumin story so far

1941

First clinical use of human albumin solution in a patient with multiple trauma and circulatory shock

[7]

1943

One of the first published reports of human albumin use in 200 patients

[50]

1975

First randomized controlled trial of human albumin in 16 patients undergoing abdominal aortic surgery

[46]

1998

Cochrane meta-analysis including 30 randomized controlled trials and reporting increased mortality rates in critically ill patients who received albumin

[2]

1998

US Food and Drug Administration issued a ‘Dear Doctor’ letter to all healthcare providers expressing serious concern over the safety of albumin administration in the critically ill population, based on the findings of the Cochrane meta-analysis, and urging physicians to exercise discretion in its use

[51]

1999

Expert Working Party of the Committee on Safety of Medicines in UK concluded that there was insufficient evidence of harm to warrant withdrawal of albumin products but large, purpose-designed, randomized, controlled clinical trials should be conducted to answer questions about mortality effects

[48]

1999

Study in 126 patients with cirrhosis and spontaneous bacterial peritonitis randomized to treatment with intravenous cefotaxime or cefotaxime and intravenous albumin; hospital and 3-month mortality rates were lower in the patients who received albumin

[52]

2001

Wilkes and Navickis’ meta-analysis including 55 trials and reporting no overall effect of albumin on mortality

[53]

2003

Meta-analysis of 90 cohort studies evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and nine prospective controlled trials evaluating use of albumin to correct hypoalbuminemia; results showed hypoalbuminemia to be a dose-dependent predictor of poor outcome and correction of serum albumin to >30 g/l associated with reduced complications

[5]

2004

Large SAFE study randomizing 6,997 patients to 4% albumin or normal saline when fluid challenge needed; results showed no difference in mortality rates among groups, and subgroup analyses suggested benefit in patients with severe sepsis and harm in those with traumatic brain injury

[49, 54, 55]

2005

US Food and Drug Administration issued a notice stating that the SAFE study had resolved the prior safety concerns raised by the Cochrane Injuries Group in 1998

[56]

2005

Results of SOAP observational study showing that albumin use was associated with decreased mortality in critically ill patients using a Cox proportional hazard model and a propensity case-matching analysis

[57]

2006

Pilot study of 100 patients with serum albumin ≤30 g/l randomized to receive 300 ml of 20% albumin solution on the first day and then 200 ml/day if their serum albumin concentration remained <31 g/l, or to receive no albumin; organ function was improved in patients treated with albumin

[30]

2011

Meta-analysis including 17 studies in patients with sepsis reporting a survival benefit for patients who received albumin

[58]

2012

ESICM taskforce Consensus statement suggesting that albumin may be included in the resuscitation of severe sepsis patients (grade 2B)

[59]

2013

Surviving Sepsis Campaign guidelines for the first time specifically suggest (grade 2C) use of albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids

[60]

2013

EARSS randomized controlled multicenter study comparing 100 ml 20% albumin with normal saline in patients with early severe sepsis, showing no differences in mortality rates between groups

[61]

2014

ALBIOS randomized controlled multicenter study comparing 20% albumin plus crystalloid or crystalloid alone and then continuing albumin infusions to maintain serum albumin ≥30 g/l; no overall difference in 28-day or 90-day mortality rates but survival benefit at 90 days in patients with septic shock

[62]