THE EFFECTS OF FENOLDOPAM ON RENAL FUNCTION AND METABOLISM IN AN OVINE MODEL OF SEPTIC SHOCK.

Abstract

The importance of renal perfusion and metabolism in septic acute kidney injury (AKI) remains unclear. Prophylactic administration of the dopaminergic agent, fenoldopam, has been suggested to reduce the occurrence of AKI, but its effects in septic shock are poorly defined. Sepsis was induced in 15 adult female sheep by injecting autologous feces into the abdominal cavity. Two hours later, the animals were randomized to one of three groups: low-dose fenoldopam (1.0 μg/kg/min, n = 5), high-dose fenoldopam (5.0 μg/kg/min, n = 5), or placebo (control, n = 5). A perivascular flow probe was placed around the renal artery and a catheter in the renal vein for measurement of renal blood flow index (RBFI) and oxygen consumption (VO2renI). Metabolism in the renal cortex was evaluated using microdialysis. Serum creatinine was measured 6-hourly and the sublingual microcirculation assessed using sidestream dark-field videomicroscopy. High-dose fenoldopam was associated with a lower RBFI at 18 h (P = 0.032) than in the control group, but VO2renI was maintained by a higher oxygen extraction (P < 0.05 vs. baseline). Sublingual microcirculatory alterations at 18 h were more severe in the high-dose than in the control and low-dose groups (P = 0.021 and P = 0.032). Renal cortex lactate and pyruvate levels increased earlier in the high-dose group than in the other two groups (P < 0.001 vs. baseline). Fenoldopam did not affect creatinine clearance or urine output. In this model of septic shock, fenoldopam did not improve renal blood flow, worsened microcirculatory alterations, and induced metabolic changes that were indicative of increased glycolysis.