UMEM Educational Pearls

Summary:

The recent ARISS (Albumin Resuscitation in Septic Shock) trial showed no difference in 90-day mortality or other secondary outcomes, similar to other trials comparing albumin and crystalloid. Notably however, the trial did not meet its predetermined enrollment requirement of patients (in the setting of the COVID-19 pandemic) and had a large portion of its intervention group failing to meet goal serum albumin level. 

The Bottom Line:

There remains no evidence-based mortality benefit of albumin over crystalloid in patients with septic shock that do not have additional indications for albumin (such as hepatorenal syndrome). Crystalloid resuscitation remains a staple of appropriate and cost-effective care in septic shock. Albumin can be considered on a case-by-case basis after standard crystalloid resuscitation in this clinical setting.

Additional Information

Background:

What is the ideal fluid for resuscitation in septic shock? Crystalloids or colloids, such as albumin?

Many trials have sought to prove albumin would be beneficial in septic shock. Some data has suggested an immune modulatory role of albumin. Additionally, albumin is thought to help maintain serum oncotic pressure to prevent further capillary leak in vasodilatory shock. A summary of some trials before ARISS are summarized below:

• SAFE trial (2003) compared 4% albumin and normal saline in the ICU setting and found no mortality difference at 28 days except a higher mortality rate in subgroup of patients with TBI. 
• CRISTAL trial (2013) looked at all crystalloids vs all colloids in septic shock in the ICU setting and found no difference in 28 day mortality. There was a non-statistically significant trend showing decreasing 90 day mortality with colloids.
• ALBIOS trial (2014) compared 20% albumin (targeting albumin level of >3g/dL) to crystalloids in the ICU setting. There was no difference in 28 and 90 day mortality but a non-statistically significant trend showing early albumin having decreased mortality.
• ICARUS-ED trial (2025) was a pilot RCT in the ED setting, comparing single 400 mL 20% albumin vs. crystalloids alone. There was no difference in SBP at 24 hours or mortality at 72 hours but a trend towards lower fluid volume and vasopressor use.

With this background, researchers in Germany sought to further evaluate albumin's role in septic shock resuscitation.

ARISS (Albumin Resuscitation in Septic Shock) Trial - Feb 2026

Patients: Adults admitted to ICUs in Germany from 10/2019 to 5/2022 that had probable or definitive evidence of infection for septic shock,  required vasopressors for at least one hour (MAP > 65 mmHg)?, had a lactate less than 18 mg/dL (2.0 mmol/L)?, and were enrolled within 24 hours of onset of septic shock. Exclusion criteria included patients that had a disease process that albumin is particularly harmful or advantageous (CHF, TBI, hepatorenal)?, pregnancy/lactation, alternative etiology of shock, and end of life care.

Intervention: All patients in intervention group received a 60-g loading dose of 20% albumin over 2-3 hours within 6-24 hrs after diagnosis of septic shock. Remainder of albumin administration was done by a resuscitation scheme to target an albumin greater than 3 g/dL while they remained alive and in the ICU.

Control: All patients in control group received crystalloid resuscitation but could receive albumin in certain situations deemed necessary (such as albumin < 1.5 g/dL).

Outcome: Primary outcome was 90-day all-cause mortality. Secondary outcomes included 28-day and 60-day mortality, ICU and hospital mortality, SOFA score change, ICU and hospital length of stay, ventilator-free and vasopressor-free days, and occurrence of adverse events.

Results: 440 patients were randomized, with 419 included in analysis. Albumin was administered in the intervention group for a median of 5 days. 15 patients received the full 28-day limit of protocol treatment with albumin. More than 50% of patients in the intervention group failed to achieve the target albumin level of greater than 3 g/dL. 90-day mortality by intention to treat analysis was 43.4% in the albumin group versus 45.9% in the control group (RR of 0.94 [95% CI, 0.76-1.17]) with no differences in subgroup analyzes. No secondary outcomes showed a statistically significant difference. There was no statistically significant difference in adverse events between groups.

Internal Validity: Enrollment did not meet need based on power calculation (estimated 1662 patients by their power calculation for a relative risk reduction of 15%. Factors affecting this included COVID-19 pandemic and a high exclusion rate for the trial enrollment of 72%. Additionally, many patients in the control group received albumin. The researchers additionally did a per-protocol analysis which also showed no statistically significant difference.

Ending Thoughts: This was a well designed trial combining elements of trials comparing albumin to crystalloids previously and using albumin to reach a defined target, similar to the ALBIOS trial. However, the lack of enrollment and not meeting their predetermined power calculation likely contributed to the results found in this trial. The trial leaves unanswered questions about albumin's role in septic shock, particularly with earlier timing and a clear concentration target.

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. Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, Preiser JC, Outin H, Troché G, Charpentier C, Trouillet JL, Kimmoun A, Forceville X, Darmon M, Lesur O, Reignier J, Abroug F, Berger P, Clec'h C, Cousson J, Thibault L, Chevret S; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013 Nov 6;310(17):1809-17. doi: 10.1001/jama.2013.280502. Erratum in: JAMA. 2013 Mar 12;311(10):1071. Régnier, Jean [corrected to Reignier, Jean]; Cle'h, Christophe [corrected to Clec'h, Christophe]. PMID: 24108515.
3. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L; 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.
4. Williams JM, Greenslade JH, Hills AZ, Ray MT. Intervention With Concentrated Albumin for Undifferentiated Sepsis in the Emergency Department (ICARUS-ED): A Pilot Randomized Controlled Trial. Ann Emerg Med. 2025 Jul;86(1):59-69. doi: 10.1016/j.annemergmed.2024.12.016. Epub 2025 Jan 23. PMID: 39846907.
5. Sakr Y, Nierhaus A, Schumacher U, Utzolino S, Jaschinski U, Petros S, Fichtner F, Eimer C, Putensen C, Tanev I, Kreienbühl L, Kluge S, Kousoulas L, Kuhn SO, Jarczak D, Quintel M, Bauer M; SepNet Critical Care Trials Group and Albumin Replacement Therapy in Septic Shock (ARISS) investigators. Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2559297. doi: 10.1001/jamanetworkopen.2025.59297. PMID: 41712212; PMCID: PMC12921518.