Prophylactic fenoldopam for renal protection in sepsis: A randomized, double-blind, placebo-controlled pilot trial

Objective: Acute renal failure is common in septic patients. Fenoldopam, a dopamine-1 receptor agonist, increases renal blood flow and may, therefore, reduce the risk of acute renal failure in such patients. Accordingly, we sought to determine the safety and efficacy of fenoldopam for the prevention of acute renal failure in septic patients. Design: Prospective, double-blind, placebo-controlled trial. Setting: Three multidisciplinary intensive care units at a university hospital. Patients: Three hundred septic patients with baseline serum creatinine concentrations < 50 mu mol/L. Interventions: We randomized patients to a continuous infusion of either fenoldopam (n = 150) at 0.09 mu g center dot kg(-1) center dot min(-1) or placebo (n = 150) while in the intensive care unit. The primary outcome measure was the incidence of acute renal failure, defined as a serum creatinine concentration increase to > 150 mu mol/L, during study drug infusion. Measurements and main results: The incidence of acute renal failure was significantly lower in the fenoldopam group compared with the control group (29 vs. 51 patients; p =.006). The odds ratio of developing acute renal failure for patients treated with fenoldopam was estimated to be 0.47 (p =.005). The difference in the incidence of severe acute renal failure (creatinine >300 mu mol/L), however, failed to achieve statistical significance (10 vs. 21; p =.056). The length of intensive care unit stay in surviving patients was significantly lower in the fenoldopam group compared with the control group (10.64 +/- 9.3 vs. 13.4 +/- 14.0; p <.001). There were no complications of fenoldopam infusion. A direct effect of treatment on the probability of death, beyond its effect on acute renal failure, was not significant (odds ratio = 0.68, p=.1). Conclusions: Compared with placebo, low-dose fenoldopam resulted in a smaller increase in serum creatinine in septic patients. The clinical significance of this finding is uncertain. A large multiple-center trial is now needed to confirm these findings.