New England Journal of Medicine
The SAFE study — a landmark RCT of 6,997 ICU patients — showed no significant difference in 28-day mortality between albumin and saline for fluid resuscitation. Establishes that crystalloid solutions are a safe, non-blood-derived alternative to albumin for volume expansion.
There was no significant difference in the rate of death between the albumin group (726 of 3,497 [20.9%]) and the saline group (729 of 3,500 [20.9%]; relative risk 0.99; 95% CI 0.91–1.09; P=0.87).