Prophylactic Fenoldopam for Renal Protection in Sepsis: Trial
Prophylactic Fenoldopam for Renal Protection in Sepsis: 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 < 150 µmol/L.
Interventions: We randomized patients to a continuous infusion of either fenoldopam (n = 150) at 0.09 µg·kg·min 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 µmol/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 µmol/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.
Sepsis is a risk factor for the development of acute renal failure (ARF), and 35-50% of ARF cases in the intensive care unit (ICU) can be attributed to sepsis. Because ARF carries a heavy burden of morbidity and mortality, its prevention is an important therapeutic goal.
To date, clinical attempts to prevent ARF in critically ill patients have focused mainly on the use of low-dose dopamine, a renal vasodilator, on the assumption that renal blood flow might be diminished in this setting. However, a large randomized controlled trial found it to be ineffective. Reasons for its lack of efficacy might relate to the high individual variability in its metabolism at any given dose, its lack of receptor selectivity, and delayed administration. Fenoldopam is a selective postsynaptic dopamine–1 receptor agonist. At doses between 0.03 and 0.1 µg·kg·min, it increases renal blood flow without modifications in systemic hemodynamics. We hypothesized that fenoldopam might be effective in preventing the development of ARF if administered before the occurrence of renal dysfunction in septic patients. We, therefore, performed a prospective randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of low-dose fenoldopam in the prevention of ARF in septic patients.
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 < 150 µmol/L.
Interventions: We randomized patients to a continuous infusion of either fenoldopam (n = 150) at 0.09 µg·kg·min 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 µmol/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 µmol/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.
Sepsis is a risk factor for the development of acute renal failure (ARF), and 35-50% of ARF cases in the intensive care unit (ICU) can be attributed to sepsis. Because ARF carries a heavy burden of morbidity and mortality, its prevention is an important therapeutic goal.
To date, clinical attempts to prevent ARF in critically ill patients have focused mainly on the use of low-dose dopamine, a renal vasodilator, on the assumption that renal blood flow might be diminished in this setting. However, a large randomized controlled trial found it to be ineffective. Reasons for its lack of efficacy might relate to the high individual variability in its metabolism at any given dose, its lack of receptor selectivity, and delayed administration. Fenoldopam is a selective postsynaptic dopamine–1 receptor agonist. At doses between 0.03 and 0.1 µg·kg·min, it increases renal blood flow without modifications in systemic hemodynamics. We hypothesized that fenoldopam might be effective in preventing the development of ARF if administered before the occurrence of renal dysfunction in septic patients. We, therefore, performed a prospective randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of low-dose fenoldopam in the prevention of ARF in septic patients.
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