A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury*

Objective: Hypoproteinemia is a common condition in critically ill patients, associated with the development of acute lung injury and acute respiratory distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide benefits lung physiology in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome, but the independent pharmacologic effects of these drugs are unknown. Design: Randomized, double-blinded, placebo-controlled multicentered trial. Setting: Eleven medical, surgical, and trauma intensive care units including 190 beds within two university hospital systems. Patients: Forty mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome, whose serum total protein concentrations were <6.0 g/dL were included. Patients were excluded for hemodynamic instability or significant renal or hepatic failure. Interventions: Subjects were equally randomly allocated to receive furosemide with albumin or furosemide with placebo for 72 hrs, titrated to fluid loss and normalization of serum total protein concentration. Measurements and Main Results: The primary outcome was change in oxygenation from baseline to day 1, with secondary physiologic and clinical outcomes. There were no differences in baseline characteristics of the subjects in relation to group assignment. Albumin-treated patients had greater increases in oxygenation (mean change in Pao2/Fio2: +43 vs. −24 mm Hg at 24 hrs and +49 vs. −13 mm Hg at day 3), serum total protein (1.5 vs. 0.5 g/dL at day 3), and net fluid loss (−5480 vs. −1490 mL at day 3) throughout the study period (all p < .05). Fluid bolus administration to control patients reduced net negative fluid balance; control patients more frequently developed hypotension and had fewer shock-free days, which translated to differences in organ failure at study end. Conclusions: The addition of albumin to furosemide therapy in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome significantly improves oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability. Additional randomized clinical trials are necessary to examine mechanisms and determine the effect on important clinical outcomes, such as the duration of mechanical ventilation.