Meta Analysis
Human albumin administration in critically ill
This review may be edited
Summary
Posted By: Gordon S. Doig
E-Mail: gdoig@med.usyd.edu.au
Posted Date: March 6th, 2001
Title: Human albumin administration in critically ill
Authors: Cochrane Injuries Group albumin Reviewers
Reference: BMJ 1998;317:235-240
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: 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.
 
Are the Results Valid?
1. Did the overview address a focused clinical question?
Unsure. The authors state their objective is to 'quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients'. 'Management of critically ill patients' is an extremely broad topic and the review would be better served to address a more focused question. For example management of hypoalbuminemia, hypotension and burns may each be complex and different enough to qualify as individual questions.
2. Were the criteria used to select articles for inclusion appropriate?
Unsure. All randomized trials of 'albumin supplementation in critically ill patients' were included however the authors also included 'pseudo-randomized trials'. It is widely accepted that most pseudo-randomized trials fail to maintain allocation concealment. Proper mantenance of allocation concealment can reduce bias by up to 40%. Trials that supplemented albumin in TPN were included along with trials that treated albumin as a pure colloid.
3. Is it unlikely that important, relevant studies were missed?
No. The literature search was very thorough and it is doubtful that important trials were missed.
4. Was the validity of the included studies appraised?
Unsure. Trials were graded for adequacy of concealment of allocation. Trials were not graded on any other methodologic criteria (e.g. blinding, presentation of complete follow-up and ITT results).
5. Were assessments of studies reproducible?
Unsure. There is no report of agreement levels (kappas) between reviewers on validity appraisal or inclusion decisions.
6. Were the results similar from study to study?
Yes. The chi-square for heterogeneity was reported as being non-significant within groups and overall.
What are the Results?
1. What are the overall results of the overview?
For burns and hypoalbuminemia, the 95% CI on relative risk of increased mortality with albumin was 1.11-5.19 and 1.07-2.67 respectively. When the poor quality trials were removed, the authors report that both CIs become non-significant (0.69-8.79 and 0.92-3.18). For hypovolemia, the increased risk of mortality with albumin was non-significant regardless of whether the poor quality trials were left in or removed (0.97-2.22 with all trials and 0.80-2.40 with only high quality trials). The authors report that the overall pooled risk is significantly increased with all trials or with only the high quality trials. Interpretation of this overall pooled risk hinges on whether you believe hypotension,burns and/or hypoalbumineamia are clinically similar and thus can be pooled.
2. How precise were the results?
The 95% CIs are discussed above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
Unsure. If the results are interpreted within indications (i.e. not pooling hypovol with hypoalb and burns) the conclusions would be much more robust. Although this paper appears to provide compelling evidence for increased risk being associated with albumin usage, due to the combination of clinically herterogeneous indications this conclusion may not be valid.
2. Were all clinically important outcomes considered?
Yes. Although it would be nice to see length of stay and costs, these are very hard to include in a meta-analysis. Mortality is probably the most important outcome in each of the clinical scenarios reviewed.
3. Are the benefits worth the harms and costs?
Unsure at this point in time.

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Human albumin administration in critically ill

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