Hyper-oncotic Albumin Reduces Mortality in ARDS Compared to Crystalloid

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (≥20%) and the iso-oncotic albumin subgroup (4%∼5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with α = 0.05 and β = 0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85,  = 0.004). RCTs ( = 204) showed no benefit (OR = 0.83,  = 0.54), but NRSs ( = 384) demonstrated reduced mortality (OR = 0.52,  = 0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40,  = 0.02) but not in RCTs (OR = 0.74,  = 0.57). Iso-oncotic albumin showed no benefit (OR = 0.88,  = 0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first ( = 0.05) and second days ( < 0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.