Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed