Albumin Therapy Does Not Cut 90-Day Death Risk in Septic Shock Patients

Septic shock is a life-threatening condition with mortality rates exceeding 40%, and there has been longstanding interest in whether albumin — beyond its oncotic role — might reduce organ dysfunction and death through anti-inflammatory, antioxidant, and nitric oxide-modulating properties. Prior data, including a subsgroup signal from the SAFE trial and a secondary analysis of the ALBIOS study, suggested a possible survival advantage for albumin in septic shock patients, motivating this dedicated trial.

The ARISS (Albumin Replacement in Septic Shock) trial was a prospective, open-label, multicenter randomized clinical trial conducted across 23 ICUs in Germany between October 2019 and May 2022. Adults diagnosed with septic shock within 24 hours were eligible; those with moribund prognosis, end-of-life decisions, or conditions where albumin is contraindicated or specifically indicated (e.g., hepatorenal syndrome) were excluded. Patients were randomized 1:1 to receive a 60-g loading dose of 20% albumin followed by daily titrated infusions (40–80 g) to maintain serum albumin ≥3.0 g/dL for up to 28 ICU days, or to standard crystalloid-based fluid management.

Of 440 randomized patients (median age 69 years; 65.9% male), 222 received albumin and 218 received standard care. Baseline characteristics were comparable between groups. The primary endpoint — 90-day all-cause mortality — was 43.3% (91/210) in the albumin group versus 45.9% (96/209) in controls, yielding a relative risk of 0.94 (95% CI, 0.76–1.17; P=.71). No statistically significant differences were observed across secondary endpoints including 28-day, 60-day, ICU, and in-hospital mortality; SOFA organ failure scores; total fluid balance; or ICU and hospital length of stay. Albumin was well tolerated with no excess adverse events attributed to treatment.

Importantly, the trial was terminated prematurely due to low enrollment rates — a consequence compounded by COVID-19 pandemic disruptions. The original sample size was powered to detect a clinically meaningful mortality reduction, and the enrolled 440 patients represent an underpowered cohort relative to that target. The authors acknowledge that the results are therefore statistically inconclusive and cannot definitively rule out a modest clinical benefit of albumin therapy.

For clinical practice, these findings suggest albumin replacement in septic shock is safe but should not be considered standard therapy based on current evidence. The authors call for additional, adequately powered RCTs — ideally with refined patient selection criteria — before albumin can be recommended or abandoned for this indication. Given the cost and resource implications of albumin infusions, equipoise remains, and clinical decision-making should continue to follow current guideline recommendations pending further evidence.