Fenoldopam Research Articles

Fenoldopam Mesylate for the Prevention of Contrast Induced Nephropathy

A randomized controlled multicenter trail was conducted to determine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures. The study measured serum creatinine levels at baseline and at 1, 24, 48 and 72 to 96 hours after drug administration. Patients (N = 315) with serum creatinine clearance of less than 60 mL/min were randomized to receive fenoldopam mesylate (n = 157) or placebo (n = 158). Twenty-eight centers participated in the study. Intravenous fenoldopam (0.05 gg/kg/min, titrated to 0.10 gg/kg/min) (or placebo) was started 1 hour prior to angiography and was continued for 12 hours. The endpoint of contrast-induced nephropathy occurred in 33.6% of the patients assigned to receive fenoldopam compared with 30.1% of patients who received the placebo. The difference in the 30-day death rate, need for dialysis, or rehospitalization between the two groups was not significant. The study concluded that fenoldopam mesylate does not prevent further ren...

Fenoldopam Mesylate and Renal Function in Patients Undergoing Liver Transplantation: A Randomized, Controlled Pilot Trial

To test the relative effects on serum creatinine (CRE), blood urea nitrogen (BUN), and urine output of small-dose dopamine and fenoldopam in patients undergoing liver transplantation, we randomized 43 patients to 1 of 2 continuous infusions over 48 h, starting with anesthesia induction: fenoldopam, 0.1 microg . kg(-1) . min(-1) or dopamine, 2 microg . kg(-1) . min(-1). We used predetermined hemodynamic and intravascular volume goals (intrathoracic blood volume index 800-1000 mL/m(2), extravascular lung water index <7 mL/kg) to manage patients with an algorithm for use of mannitol and furosemide to maintain urine output >1 mL . kg(-1) . h(-1). At postoperative day 3, the median CRE increase was 0.2 mg/dL (interquartile range [IQR] -0.2-0.5) with fenoldopam and 0.5 mg/dL (IQR 0.3-0.9, P = 0.004) in the dopamine group. The BUN increase was median 2 mg/dL (IQR -2-8) versus 8.5 mg/dL (IQR 5-12, P = 0.01), respectively, with fenoldopam versus dopamine. Urine output was similar; however, significantly fewer fenoldopam patients required furosemide compared with dopamine patients (median 1 [IQR 0-3] versus 3 [IQR 2-4], respectively, P = 0.003). The hemodynamic effects of dopamine and fenoldopam were similar. Compared with dopamine, in the setting of liver transplantation, fenoldopam is associated with better CRE and BUN values.

Fenoldopam Mesylate for the Prevention of Contrast-Induced Nephropathy

Survey of Anesthesiology: October 2004 - Volume 48 - Issue 5 - p 271-273 doi: 10.1097/01.sa.0000140564.44158.f9

Fenoldopam Prophylaxis of Postoperative Acute Renal Failure in High-Risk Cardiac Surgery Patients

Background Acute renal failure requiring replacement therapy occurs in 1% to 2% of patients who have undergone cardiac surgery with cardiopulmonary bypass and is associated with a very high mortality rate. The aim of this study was to determine if prophylactic treatment with fenoldopam mesylate of patients at high risk of postoperative acute renal failure reduced the incidence of this event. Methods This was a multicenter, prospective, cohort study in which 108 patients at high risk of postoperative acute renal failure and undergoing cardiac surgery with cardiopulmonary bypass were treated with fenoldopam mesylate (0.08 μg · kg −1 · min −1) starting at the induction of anesthesia and throughout at least the next 24 hours. A homogeneous control group of 108 patients was created using a propensity-score analysis. Results Fenoldopam prophylaxis was significantly associated with a reduction in acute renal failure incidence (from 22% to 11%, p = 0.028), a less pronounced creatinine clearance decrease ( p = 0.05), and a lower mortality rate (6.5% versus 15.7%, p = 0.03) by the univariate analysis, but these results were not confirmed by a multivariable analysis. Within the subgroup of patients who suffered a postoperative low output syndrome, fenoldopam prophylaxis was an independent protective factor for postoperative renal failure (odds ratio, 0.14; 95% confidence interval, 0.03 to 0.7; p = 0.017). Conclusions Given the limitations of a nonrandomized prospective trial, our results support the hypothesis that fenoldopam may reduce the risk of acute renal failure in patients in whom endogenous and exogenous cathecolamines action may induce a renal vascular constrictive condition.

N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity

We performed a study to assess the efficacy of fenoldopam mesylate (a specific agonist of the dopamine-1 receptor) as compared with N-acetylcysteine (NAC) in preventing contrast agent-associated nephrotoxicity (CAN). Prophylactic administration of NAC, along with hydration, prevents CAN in patients with chronic renal insufficiency who are undergoing contrast media administration. Preliminary data support the hypothesis that fenoldopam might be as effective as NAC. One hundred ninety-two consecutive patients with chronic renal insufficiency, referred to our institution for coronary and/or peripheral procedures, were assigned randomly to receive 0.45% saline intravenously and NAC (1,200 mg orally twice daily; NAC group; n = 97) or fenoldopam (0.10 microg/kg/min; fenoldopam group; n = 95) before and after a nonionic, iso-osmolality contrast dye administration. Baseline creatinine levels were similar in the two groups: NAC group = 1.72 mg/dl (interquartile range, 1.55 to 1.90 mg/dl) and fenoldopam group = 1.75 mg/dl (interquartile range, 1.62 to 2.01 mg/dl) (p = 0.17). An increase of at least 0.5 mg/dl of the creatinine concentration 48 h after the procedure occurred in 4 of 97 patients (4.1%) in the NAC group and in 13 of 95 patients (13.7%) in the fenoldopam group (p = 0.019; odds ratio 0.27; 95% confidence interval 0.08 to 0.85). The amount of contrast media administration was similar in the two groups (NAC group = 160 +/- 82 ml; fenoldopam group = 168 +/- 104 ml; p = 0.54). N-acetylcysteine seems to be more effective than fenoldopam in preventing CAN.

D 5 dopamine receptor regulation of reactive oxygen species production and blood pressure in mice

OR-45 Key Words: D5 Receptor, Reactive Oxygen Species, Hypertension

Fenoldopam Mesylate Fails to Prevent Contrast-Inducted Nephropathy

Nearly half of patients with preexisting renal insufficiency or diabetes mellitus who undergo angiography develop contrast-induced nephropathy after

Fenoldopam Does Not Prevent Contrast-Induced Nephropathy

For patients with renal insufficiency who undergo coronary angiography, contrast-induced nephropathy is a common complication. Fenoldopam mesylate, a

Management of hypertension emergencies.

Although they have become less common, hypertensive emergencies occur with an incidence of approximately 1 to 2/100,000 people per year. Our knowledge about this problem, its pathophysiology, risk factors, and appropriate treatment options has expanded during the past decade. A hypertensive emergency can be declared when an elevated blood pressure is associated with acute target-organ damage. Rapid evaluation and treatment (typically with an intravenously administered agent) should be instituted, usually in an intensive care unit setting, and the patient should be observed carefully during acute blood-pressure lowering. When properly treated, the prognosis for these patients is not nearly as dismal as it was more than 60 years ago, and the initial level of function of target organs (brain, heart, kidneys) is more indicative of an emergency than the actual level of blood pressure. Therapeutic options include the time-tested sodium nitroprusside (which has toxic metabolic products and is contraindicated in pregnancy, tobacco amblyopia, and Leber's optic atrophy); fenoldopam mesylate; and nicardipine. When properly treated, "malignant hypertension" need be considered malignant no longer.

Randomized comparison of fenoldopam and N-acetylcysteine to saline in the prevention of radio-contrast induced nephropathy

Randomized comparison of fenoldopam and N-acetylcysteine to saline in the prevention of radio-contrast induced nephropathy

A prospective, randomized placebo-controlled multicenter trial evaluating fenoldopam mesylate for the prevention of contrast induced nephropathy: The CONTRAST trial

A prospective, randomized placebo-controlled multicenter trial evaluating fenoldopam mesylate for the prevention of contrast induced nephropathy: The CONTRAST trial

A case series of low-dose fenoldopam in seventy cardiac surgical patients at increased risk of renal dysfunction

Objective: To evaluate the usefulness of low-dose fenoldopam mesylate in patients at risk of developing renal dysfunction after cardiac surgery requiring cardiopulmonary bypass. Design: A prospective, single-center, observational study. Setting: University teaching hospital. Participants: Seventy patients scheduled for elective cardiac surgery with one or more predefined risk factors for renal dysfunction. Interventions: After induction of anesthesia, fenoldopam (0.03 μg/kg/min) was administered throughout surgery and into the postoperative period, until the patient was stable and weaned from all other vasoactive agents. Perioperatively, fenoldopam was also used as a second-line antihypertensive agent as required. Measurements and Main Results: No patient developed renal failure that required dialysis, whereas 7.1% (5/70) developed non–dialysis-dependent renal dysfunction. Four out of these 5 patients had 2 or more risk factors (9.5%). Higher preoperative creatinine levels, a history of hypertension, myocardial infarction within 5 days of surgery, and a preoperative diagnosis of chronic renal insufficiency were all good predictors of postoperative non–dialysis-dependent renal dysfunction. Discharge serum creatinine levels were lower than preoperative levels (1.16 ± 0.36 mg/dL v 1.26 ± 0.34 mg/dL, p < 0.05). Conclusion: These findings suggest that renal function was preserved in patients at increased risk for renal dysfunction after cardiac surgery when low-dose fenoldopam was used in the perioperative period. However, a randomized, controlled trial is required to establish efficacy. Copyright 2003, Elsevier Science (USA). All rights reserved.

Compatibility of fenoldopam mesylate with other drugs during simulated Y-site administration.

Compatibility of fenoldopam mesylate with other drugs during simulated Y-site administration.

Using a dopamine type 1A receptor agonist in high-risk patients to ameliorate contrast-associated nephropathy.

The objective of our study was to evaluate the effects of fenoldopam mesylate, a dopamine type 1A receptor agonist and a potent renal vasodilator that markedly increases renal blood flow, on kidney function of patients who were receiving iodinated contrast material for an interventional procedure and thought to be at high risk of contrast-associated nephropathy. We retrospectively reviewed the records of all patients who received fenoldopam mesylate to determine the acute and, when possible, the longer term effects on kidney function. Twenty-nine cases were reviewed. The average serum creatinine value before contrast administration was 2.55 mg/dL (range, 1.3-5.8 mg/dL) [corrected]. Twenty-four hours after contrast administration, serum creatinine was measured in 28 of the 29 patients. The serum creatinine values had decreased in 16 of the 28 patients by an average of 0.55 mg/dL [corrected]. In nine patients, the serum creatinine value had not changed. Two of the three increases in the serum creatinine value appear to have been caused primarily by problems that did not involve the contrast material. The use of fenoldopam mesylate at appropriate doses offers patients at high risk for contrast-associated nephropathy a chance to avoid this complication. To learn the extent and true nature of the effect of fenoldopam mesylate in this patient population requires a rigorous scientific trial, which is currently underway.

Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion: A pilot trial in the prevention of contrast nephropathy

Background Radiocontrast nephropathy (RCN) is a common source of acute renal failure in hospitalized patients and is associated with increased morbidity and mortality rates. Fenoldopam mesylate is a dopamine A1 receptor agonist that augments renal plasma flow (RPF) in patients with normotensive and hypertensive conditions. To determine whether fenoldopam mesylate attenuates reductions in RPF after contrast infusion, we conducted a double-blind, randomized, placebo-controlled pilot trial of fenoldopam mesylate in patients who underwent contrast angiography. Methods Fifty-one patients with chronic renal insufficiency (creatinine level, 2.0-5.0 mg/dL) who were undergoing contrast angiography were screened, and 45 patients were randomized to receive normal saline solution (1/2 NS) or 1/2 NS plus fenoldopam mesylate at 0.1 μg/kg/min at lease 1 hour before infusion with contrast dye. Serum creatinine level was measured at baseline and at 24, 48, and 72 hours after angiography. The primary endpoint was change in RPF 1 hour after contrast infusion. The secondary endpoint was incidence of RCN, defined as a 0.5 mg/dL or a 25% rise in serum creatinine level at 48 hours. Results RPF at 1 hour after angiography was 15.8% above baseline in the fenoldopam mesylate group compared with 33.2% below baseline in the 1/2 NS group (P <.05). The incidence rate of RCN at 48 hours was 41.0% in the 1/2 NS group versus 21% in the fenoldopam mesylate group (P =.148). Among patients with diabetes, the incidence rate of RCN tended to be higher in the 1/2 NS group compared with the fenoldopam mesylate group (64% vs 33%; P =.14). The peak serum creatinine level at 72 hours after contrast infusion was significantly higher at in the 1/2 NS group (creatinine level, 3.6 ± 1.0 mg/dL) compared with the fenoldopam mesylate group (creatinine level, 2.8 ± 0.35 mg/dL; P <.05). RPF was significantly (P <.0001) reduced in patients with RCN compared with patients in whom RCN did not develop. Conclusion The results of this pilot trial suggest that fenoldopam mesylate is a promising prophylactic agent for RCN and that larger multicenter trials should be conducted to prove its efficacy. (Am Heart J 2002;143:894-903.)

Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside.

Fenoldopam is a novel dopamine-1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro-denervated animal models. A total of 60 New Zealand white rabbits were divided into two groups of 30 each: the neuraxis-intact group and the totally baro-denervated group. Each group was further divided into three groups of 10 each to receive SNP 10 microg x kg(-1), FM 10 microg x kg(-1) or FM 20 microg x kg(-1), respectively. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded before and after intravenous (i.v.) administration of each agent. In addition, cardiac and sympathetic baroreflex sensitivity were assessed in the neuraxis-intact animals. In the neuraxis-intact groups, although RSNA was increased to a similar extent in all three groups (P<0.01), the reduction of MAP with FM groups was significantly greater than with SNP (P<0.05). HR was increased only in the SNP group. Cardiac (HR) and sympathetic barosensitivity were significantly attenuated with FM 20 microg x kg(-1) as compared to the SNP group. In the baro-denervated groups, there were significant and similar degrees of reduction of MAP in all three group up to 1 min (P<0.01). MAP remained significantly decreased in the FM groups for 10 min (only 2 min with SNP) in both animal models. Unlike sodium nitroprusside, fenoldopam attenuates both cardiac (heart rate) and sympathetic baroreflex sensitivity, which may explain the lack of rebound hypertension with fenoldopam. The offset of hypotensive effects of fenoldopam is a significantly slower process as compared to nitroprusside, and this may be an unfavorable feature of fenoldopam should overshoot of hypotension occur.

Fenoldopam in the Prevention of Contrast Media–Induced Acute Renal Failure

Fenoldopam in the Prevention of Contrast Media–Induced Acute Renal Failure

Renal blood flow changes induced with endothelin-1 and fenoldopam mesylate at quantitative Doppler US: initial results in a canine study.

To evaluate quantitative Doppler ultrasonography (US) for assessing renal blood flow changes induced with endothelin-1 (ET-1) and fenoldopam mesylate in conscious dogs. A blood flow probe was surgically implanted around the renal artery in eight adult dogs. Color and power Doppler US images were acquired in conscious restrained dogs during intravenous infusion of ET-1 and fenoldopam mesylate. Simultaneous with imaging, blood flow through the renal artery was measured with the implanted probe. The color level of the images within the region representing the kidney was analyzed to derive flow indices. These indices were compared with direct-flow measurements. The flow indices, color-weighted flow area (CWFA), and percentage of area of color, derived from color and power Doppler US images, correlated linearly with direct flow. The mean color level of color and power Doppler US images correlated weakly with direct flow. Pre- versus postinfusion CWFA decreased with all ET-1 infusions (P < or =.032). Infusion of fenoldopam mesylate increased CWFA in all cases (P < or =.032). Quantitative Doppler US enabled successful measurement of the flow changes induced with ET-1 and fenoldopam mesylate. Quantitative Doppler US is potentially useful as a noninvasive surrogate endpoint in evaluating the action of various therapeutic agents.

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs.

It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. Prospective, randomized, controlled experiment. University-based animal laboratory and research unit. Eight female beagle dogs. Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.

Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.