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Important Safety Information on Albumin Therapy in Critically-ill Patients - Notice to Hospitals
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(PDF Version - 53 K)Contact MHPD
August 16, 2005
To: Hospital Chief of Medical Staff
Please distribute to the relevant Departments of Surgery; Emergency Medicine; Internal Medicine; Intensive Care; Oncology; Gastroenterology; Nephrology; Burn Unit; Neurosurgery; the Blood Bank and other involved professional staff and post this NOTICE in your institution.
Subject: Albumin therapy in critically-ill patients.
Health Canada wishes to communicate an update to previous safety information regarding the use of albumin for fluid resuscitation in critically-ill patients.
- A recent large, randomized study (SAFE) indicates that albumin neither increases nor decreases mortality in hypovolaemic patients.
- As burn patients were not included in the SAFE study, the safety concerns raised by a 1998 meta-analysis concerning the use of albumin in these patients have not been resolved.
- Further studies will be needed to assess the safety of albumin use in other patient subgroups including those with traumatic brain injury.
- Health care professionals are reminded that when albumin is to be given, the recommendations in the authorized product information, including indications, contraindications, warnings and precautions, adverse effects and dosage are to be followed.
On August 7, 1998, Health Canada issued a Notice to Hospitals http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_1998/albumin_nth-ah-eng.php providing information regarding a publication from the Cochrane Injuries Group in the July 25, 1998 issue of the British Medical Journal1. That article was a meta-analysis review of 32 published clinical trials examining the effects of albumin treatment for seriously-ill patients with hypovolaemia and/or hypoalbuminemia such as with acute blood loss or burns. The results of this analysis suggested that patients treated with albumin had a 6% increased risk of dying compared to those treated with other intravenous fluids. It was uncertain whether the albumin could be responsible for these deaths, or why it might be harmful. Health care professionals were reminded at that time that more research was needed in order to assess the use of albumin, but that when used, the recommendations in the authorized product information were to be closely followed.
On May 27, 2004, the New England Journal of Medicine published the results of SAFE (Saline versus Albumin Fluid Evaluation)2, a large randomized trial comparing 4% albumin with normal saline for fluid resuscitation of intensive care unit patients, with a primary outcome measure of death from all causes at 28 days. Almost 7000 patients participated in the trial, and for patients receiving albumin, the risk of death was the same as for those receiving saline (relative risk 0.99, 95% confidence interval 0.91 to 1.09), thereby resolving the safety issues that were raised in 1998. However, burn patients were not included in that study and exploratory analysis of the sub-group of trauma patients indicated that in those with concomitant brain injury, mortality with albumin was increased (relative risk 1.36, 95% confidence interval 0.99 to 1.86, p=0.04). For patients with sepsis, a higher survival rate was seen in the albumin group, but this was not statistically significant (relative risk 0.87, 95% confidence interval 0.74 to 1.02, p=0.09), and the clinical importance of this observation is not clear. It should be noted that the study was not powered to detect differences between subgroups and that such differences may occur by chance.
A new meta-analysis from the Cochrane Injuries Group3, published October 18, 2004 and including the SAFE study as well as additional studies now indicates that when albumin is used for hypovolaemia, the relative risk of dying is 1.01 (95% confidence interval 0.92 to 1.10), and therefore albumin neither increases nor decreases mortality in these patients.
Whether the use of albumin brings additional benefits or risks to specific patient subgroups or not will have to be determined by specifically designed and adequately powered studies.
The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Any occurrences of other serious and/or unexpected adverse reactions in patients receiving albumin should be reported to Health Canada at the following address:
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
For other inquiries, please refer to contact information:
Marketed Health Products Directorate
MHPD_DPSC@hc-sc.gc.ca
Tel: (613) 954-6522
Fax: (613) 952-7738
The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
References:
1Cochrane Injuries Group Albumin Reviewers, 1998. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ. 317(7153):235-40.
2The SAFE study Investigators, 2004. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 350(22):2247-56.
3The Albumin Reviewers. Human albumin solution for resuscitation and volume expansion in critically ill patients. The Cochrane Database of Systematic Reviews, 2004 Oct 18;(4) CD001208.
