Albumin Replacement in Patients with Severe Sepsis or Septic Shock

BackgroundAlthough previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. MethodsIn this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. ResultsDuring the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. ConclusionsIn patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.) In patients with severe sepsis, albumin replacement in addition to crystalloid administration conferred no benefit, as compared with crystalloids alone, with respect to mortality at 28 or 90 days. Post hoc analysis suggested a possible benefit in patients with septic shock. For decades, human albumin has been administered to patients to provide adequate oncotic pressure and intravascular volume.(1) In 1998, however, a report from the Cochrane Injuries Group Albumin Reviewers indicated that the administration of albumin may be potentially harmful in critically ill patients, as compared with the administration of crystalloid solutions.(2) Subsequent meta-analyses reported contradictory findings.(3),(4) To clarify this issue, a large, double-blind, randomized trial (the Saline versus Albumin Fluid Evaluation [SAFE] study)(5) was conducted, in which 4% albumin solution was compared with normal saline as fluid replacement in critically ill patients, with results indicating that albumin administration was ...