Abstract
Purpose
To determine the effect of random assignment to fluid resuscitation with albumin or saline on organ function and mortality in patients with severe sepsis.
Methods
Pre-defined subgroup analysis of a randomized controlled trial conducted in the intensive care units of 16 hospitals in Australia and New Zealand.
Results
Of 1,218 patients with severe sepsis at baseline, 603 and 615 were assigned to receive albumin and saline, respectively. The two groups had similar baseline characteristics. During the first 7 days mean arterial pressure was similar in the two groups, but patients assigned albumin had a lower heart rate on days 1 and 3 (p = 0.002 and p = 0.03, respectively) and a higher central venous pressure on days 1–3 (p < 0.005 each day). There was no difference in the renal or total Sequential Organ Failure Assessment score of the two groups; 113/603 (18.7%) of patients assigned albumin were treated with renal replacement therapy compared to 112/615 (18.2%) assigned saline (p = 0.98).
The unadjusted relative risk of death for albumin versus saline was 0.87 [95% confidence interval (CI) 0.74–1.02] for patients with severe sepsis and 1.05 (0.94–1.17) for patients without severe sepsis (p = 0.06 for heterogeneity). From multivariate logistic regression analysis adjusting for baseline factors in patients with complete baseline data (919/1,218, 75.5%), the adjusted odds ratio for death for albumin versus saline was 0.71 (95% CI: 0.52–0.97; p = 0.03).
Conclusions
Administration of albumin compared to saline did not impair renal or other organ function and may have decreased the risk of death.
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Acknowledgments
Funding bodies are listed alphabetically (Australia unless otherwise stated): Auckland District Health Board, New Zealand; Australian Commonwealth Department of Health and Aged Care; CSL Limited, Melbourne, Victoria; Middlemore Hospital, New Zealand; Australian National Health and Medical Research Council; Health Department of Western Australia; Health Research Council of New Zealand; New South Wales Health Department; Northern Territory Health Services; Queensland Health Services Department; Royal Hobart Hospital, Tasmania; South Australian Department of Human Services; Victorian Department of Human Services. The funding bodies played no part in the conduct or analysis of the study, or the decision to publish the results.
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Authors and Affiliations
Consortia
Additional information
The Saline versus Albumin Fluid Evaluation (SAFE) Study is a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG), the Australian Red Cross Blood Service, and the George Institute for International Health. The writing committee (Simon Finfer, Suzanne McEvoy, Rinaldo Bellomo, Colin McArthur, John Myburgh, and Robyn Norton) takes responsibility for the content of this article. The SAFE Study Investigators are listed in full in the Appendix.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Appendix: SAFE Study Investigators
Appendix: SAFE Study Investigators
Writing Committee
Simon Finfer (Chair), Suzanne McEvoy, Rinaldo Bellomo, Colin McArthur, John Myburgh and Robyn Norton.
SAFE Study Management Committee
Robyn Norton (Chair), Julie French (Senior Project Manager), Rinaldo Bellomo, Simon Finfer, John Myburgh, Suzanne McEvoy, Gordon Doig, Mary Hayek and Sheridan O’Donnell.
SAFE Study Steering Committee
Simon Finfer (Chair), Anthony Bell, Rinaldo Bellomo, Neil Boyce, David Blythe, John Cade, Marianne Chapman, Louise Cole, D. James Cooper, Andrew Davies, Craig French, Julie French, Christopher Joyce, Colin McArthur, Stephen MacMahon, John Myburgh, Bruce Neal, Robyn Norton, Jeffrey Presneill, Peter Saul, Ian Seppelt, Dianne Stephens, Andrew Turner, Anthony Williams and Clive Woolfe.
SAFE Study External Safety and Data Monitoring Committee
Richard Peto (Chair), Peter Sandercock, Charles Sprung and J. Duncan Young.
Statistical analysis
The George Institute for International Health, University of Sydney, NSW.
Laurent Billot, Michael Fitzharris, Qiang Li, Suzanne McEvoy.
Site investigators
Alphabetically by institution and surname, Australia unless stated, NSW = New South Wales, NZ = New Zealand.
Alfred Hospital, Melbourne, Victoria: Julie Charlton, James Cooper, Andrew Davies, Catherine Harry, Lisa Higgins, Katherine Moulden, Shirley Vallance.
Auckland Hospital, Auckland (NZ): Janine Chadderton, Lynette Newby, Colin McArthur.
Austin & Repatriation Medical Centre, Melbourne, Victoria: Samantha Bates, Rinaldo Bellomo, Donna Goldsmith, Alison Voss.
Australian Red Cross Blood Service, Melbourne, Victoria: Neil Boyce.
Fremantle Hospital, Fremantle, Western Australia: David Blythe, Annamaria Palermo.
The George Institute for International Health, University of Sydney, NSW: Lesley Francis, Julie French, Michael Fitzharris, Mary Hayek, Kathy Jayne, Stephen MacMahon, Mamta Merai, Bruce Neal, Robyn Norton, Sameer Pandey, Sheridan O’Donnell, Manuela Schmidt, Siva Sivarajasingham, Mark Woodward.
John Hunter Hospital, Newcastle, NSW: Rosemary Carroll, Brett McFadyen, Peter Saul.
Middlemore Hospital, Auckland (NZ): Jane Clarke, Juliet Powell, Anthony Williams, Judi Tai.
Nepean Hospital, Penrith, NSW: Louise Cole, Iveta Hynesova, Ian Seppelt, Leonie Weisbrodt.
Princess Alexandra Hospital, Brisbane, Queensland: Lisa Bradley, Christopher Joyce, Theresa Kelly, Anthony Limpus, Robyn Moore.
Royal Adelaide Hospital, South Australia: Marianne Chapman, Stephanie Creed, Sandra Kaplan, Justine Rivett.
Royal Darwin Hospital, Northern Territory: Dianne Stephens, Jane Thomas.
Royal Hobart Hospital, Tasmania: Anthony Bell, Kathy Marsden, Andrew Turner.
Royal Melbourne Hospital, Victoria: Catherine Boyce, John Cade, Belinda Howe, Jeffrey Presneill, Megan Robertson.
Royal North Shore Hospital, Sydney, NSW: Gordon Doig, Simon Finfer, Anne O’Connor, Julie Potter, Naresh Ramakrishnan.
Royal Prince Alfred Hospital, Sydney, NSW: Catherine Powell, Dorrilyn Rajbhandari, Clive Woolfe.
St George Hospital, Sydney, NSW: Kathryn Girling, Marie Hodgetts, Alina Jovanovska, John Myburgh.
Western Hospital, Melbourne, Victoria: Craig French, Lorraine Little.
Competing interests and the role of SAFE study funders:
The SAFE study was part funded by CSL Limited. CSL Limited has acted as a sponsor for scientific meetings of the Australian and New Zealand Intensive Care Society and its Clinical Trials Group. CSL Limited has paid travel expenses for Professor Simon Finfer and Professor Rinaldo Bellomo to present the results of the SAFE study at scientific and industry sponsored meetings. In common with the other funders of the SAFE study, CSL Limited had no say in the design or conduct of the study, and no role or say in the analysis of the results, the preparation of manuscripts or the decision to submit results for publication.
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The SAFE Study Investigators. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 37, 86–96 (2011). https://doi.org/10.1007/s00134-010-2039-6
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DOI: https://doi.org/10.1007/s00134-010-2039-6