Whether albumin is associated with reduced mortality in the resuscitation of severe sepsis and septic shock compared with crystalloid is a matter of debate.
The Saline versus Albumin Fluid Evaluation (SAFE) study revealed that there is no difference in 28-day mortality between patients who received albumin versus saline in the intensive care unit as fluid of resuscitation [1]. However, a predefined subgroup analysis of patients with severe sepsis in the same study suggested that albumin potentially resulted in a lower 28-day mortality (30.7% versus 35.3%) in patients with severe sepsis without causing impairment in renal or other organ function [2].
The EARSS trial analyzed the efficacy and tolerance of hyperoncotic albumin administration in septic shock patients in 29 centers in France. The study is only available in an abstract published in the intensive care medicine journal in 2011 and not been published in its entirety. The study revealed that vasopressor-free days were higher in albumin group but 90-day mortality was not statistically different between the two groups (24.1% versus 26.3%) [3].
A large randomized controlled trial, the ALBumin Italian Outcome Sepsis (ALBIOS), reported no 28-day or 90-day mortality benefit among 1818 patients with severe sepsis and septic shock when the albumin level was maintained above 30 g/L [4]. During the first seven days the albumin group had a significantly lower cumulative net fluid balance (median 347 mL vs. median 1220 mL; p = 0.004) and quicker resolution of shock (median days to suspension of vasopressors 3 vs. 4; p = 0.007). The post hoc analysis of the septic shock subgroup in 1,121 patients of the same study supported a survival benefit to albumin. The 90-day mortality was 43.6% in the albumin group compared to 49.9% in the crystalloid group (p= 0.03).
A single center, randomized, controlled study in cancer patients (The Lactated Ringer Versus Albumin in Early Sepsis Therapy (RASP) revealed that adding albumin to early standard resuscitation with lactated Ringer's was not associated with improved 7-day or 28-day mortality and it did not affect the renal replacement therapy needs [5].
Multiple meta-analyses with studies comparing albumin versus crystalloids looked at mortality outcome and the need for renal replacement therapy (RRT). Some of the studies included general critically-ill patients and used fresh frozen plasma rather than albumin. Despite the suggestion of some meta-analyses of improved mortality with albumin administration in sepsis, a Cochrane review which included 10 RCTs with 12,492 patients comparing albumin versus crystalloids found no difference in 30-day (RR, 0.98; 95% CI, 0.93−1.06) or 90-day mortality (RR, 0.98; 95% CI, 0.92−1.04) or the need for RRT between groups (RR, 1.11; 95% CI, 0.96−1.27) [6].
A meta-analysis in patients with septic shock published in Sao Paulo Med J revealed that albumin did not decrease all-cause mortality at the final follow-up. However, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings.
The randomized controlled multicenter study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. The study protocol is published in 2020 and no preliminary results are available yet.
In conclusion, it is not final yet whether albumin as a resuscitative fluid improves outcome in patients with septic shock or not. However, given its high cost and based on the recommendations of the 2021 International Guidelines for Management of Sepsis and Septic Shock (Surviving Sepsis Campaign), the following recommendation can be followed:
For adults with sepsis or septic shock, it is suggested to use albumin in patients who received large volumes of crystalloids over using crystalloids alone. Weak recommendation, moderate quality of evidence [8].
REFERENCES
1. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56. doi: 10.1056/NEJMoa040232. PMID: 15163774.
2. SAFE Study Investigators, Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011 Jan;37(1):86-96. doi: 10.1007/s00134-010-2039-6.
3. Charpentier J, Mira JP, Group ES. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study. Intensive Care Med 2011;37(suppl 1):S115.
4. Caironi P, et al. ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014 Apr 10;370(15):1412-21. doi: 10.1056/NEJMoa1305727. Epub 2014 Mar 18. PMID: 24635772.
5. Park CHL, et al. Lactated Ringer's Versus 4% Albumin on Lactated Ringer's in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial. Crit Care Med. 2019 Oct;47(10):e798-e805. doi: 10.1097/CCM.0000000000003900. PMID: 31356475.
6. Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018 Aug 3;8(8):CD000567. doi: 10.1002/14651858.CD000567.pub7. PMID: 30073665; PMCID: PMC6513027.
7. Zou Y, Ma K, Xiong JB, Xi CH, Deng XJ. Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis. Sao Paulo Med J. 2018 Sep-Oct;136(5):421-432. doi: 10.1590/1516-3180.2017.0285281017. PMID: 30570093.
8. Sakr Y, et al - Critical Care Trials Group. Randomized controlled multicenter study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial. Trials. 2020 Dec 7;21(1):1002. doi: 10.1186/s13063-020-04921-y. PMID: 33287911; PMCID: PMC7720035.
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