Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: A systemic, splanchnic and renal hemodynamic study

Abstract

We studied the effects of fenoldopam, a selective dopamine DA1 agonist on systemic and splanchnic hemodynamics, renal blood flow and sodium excretion in 12 patients with alcoholic cirrhosis and ascites. Hepatic, azygos and renal veins were catheterized before and after intravenous administration of fenoldopam, 0.05 micrograms/kg/min for 1 hr and increased to 0.1 micrograms/kg/min for another hour. Mean arterial pressure progressively decreased (from 83 +/- 7 to a minimum of 77 +/- 8 mm Hg 100 min after starting the infusion) but returned to baseline level at 120 min. Plasma norepinephrine and renin activity increased (respectively from 567 +/- 297 to 919 +/- 375 pg/ml, p less than 0.05, and from 17 +/- 14 to 23 +/- 15 ng/ml/hr, p less than 0.05). Renal blood flow, urine output or sodium excretion did not change. Sodium output decreased at 1 hr from 6.9 mumol/min to 4.0 mumol/min, p less than 0.05. Both hepatic venous pressure gradient and azygos blood flow significantly increased by 21%. We conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites. In addition, dopamine DA1 agonism caused further increases in norepinephrine concentration and plasma renin activity. Portal pressure also increased, probably because of an increase in mesenteric blood flow. These results question the renal benefit and raise concern about the use of dopamine agonists in patients with cirrhosis and ascites.

Hepatic Blood Flow and Splanchnic Oxygen Consumption in Patients With Liver Failure. Effect of High–Volume Plasmapheresis

“…To compare the magnitude of the estimated HBF with values reported by others, 17 studies comprising a total of 270 patients with cirrhosis was looked through. 1,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In these studies, ICG was used and the hepatic extraction was measured and taken into account in the calculations. The median (of the reported mean HBF in the individual studies) was 1.18 L/min (range 0.93-1.90).…”

Endogenous dopaminergic activity in Child–Pugh A cirrhosis: potential role in renal sodium handling and in the maintenance of clinical compensation

“…In cirrhotic patients, low-dose infusion of dopamine (1-3 g min -1 kg -1 body weight) causes a significant increase in renal blood flow [10], glomerular filtration rate, urine output and sodium excretion [11], but the effects of exogenously administered dopamine have been questioned [12].…”

Dopamine under α1-blockade, but not dopamine alone or fenoldopam, increases depressed gastric mucosal oxygenation*

“…This discrepancy has been demonstrated for dopamine (8,11,12) and dopexamine (10,13), whereas for fenoldopam little information is available. Under compromised cardiocirculatory conditions, fenoldopam may elicit beneficial splanchnic effects [e.g., increase splanchnic perfusion during hemorrhage (4) and heart failure (14)], maintain splanchnic conditions [e.g., during endotoxemia (12), after cardiopulmonary bypass (15) and in hypertensive states (16)], or even exert negative splanchnic effects [e.g., increase portal venous pressure (17) and decrease liver function (18) …”