The Committee on Safety of Medicines has advised doctors to restrict the use of, and take special care when using, human albumin after concerns that far from saving life the preparation may actually increase mortality.
A systematic review by the Cochrane Group published last year (BMJ 1998;317:253-40) of 23 randomised controlled trials, including 1419 critically ill patients with hypovolaemia, burns, and hypoalbuminaemia, found that the risk of death in the group treated with albumin was significantly higher than in patients who received either crystalloids or no treatment.
The relative risk of death was 1.46 (confidence interval 0.97 to 2.22) for hypovolaemia, 2.40 (1.11 to 5.19) for burns, and 1.69 (1.07 to 2.67) for hypoalbuminaemia. The pooled difference in the risk of death with albumin was 6%(3%to 9%).
Ian Roberts of the Institute of Child Health, London, who carried out the review, which attracted numerous protests, emphasised at the time that the results must be interpreted with caution because the trials were relatively small and involved only a limited number of deaths. But he also pointed out that 100000 patients receive human albumin in the United Kingdom each year and warned: “The really worrying thing is that if these results apply to just 10%of these patients, six deaths per 100 would work out at 600 deaths a year. This could be one of the biggest medical disasters in a long time.”
An expert working group set up by the Committee on Safety of Medicines to examine the findings has now concluded, however, that there is “insufficient evidence of harm to warrant withdrawal of albumin products from the market” and that the effect of albumin on mortality can “only be answered by conducting large, purpose designed, randomised, controlled clinical trials.”
Nevertheless, it has recommended that the indication for human albumin solutions should focus on the use of albumin to replace lost fluids rather than the underlying illness resulting in hypovolaemia and that hypo-albuminaemia in itself is not an appropriate indication.
The working group’s recommendations—published on 11 June in Current Problems in Pharmacovigilance—add that product information should contain warnings about the risks of hypervolaemia and cardiovascular overload and emphasise that monitoring in patients receiving albumin should be undertaken.
Figure.
QUEST/SCIENCE PHOTO LIBRARY
Albumin: possible association with increased mortality