Society of Cardiovascular Anesthesiologists

Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial.

Bove T, Landoni G, Calabro MG, Aletti G, Marino G, Cerchierini E, Crescenzi G, Zangrillo A. Circulation. 2005 Jun 21; 111(24):3230-5.

Reviewer: Mohammed Minhaj, MD
University of Chicago
Chicago, IL

Abstract: Postoperative acute renal failure (ARF) is a serious complication of cardiac surgery resulting in increased morbidity, mortality and hospital stay. The authors of this study attempted to determine if prophylactic use of fenoldopam, a specific dopamine-1 receptor agonist would reduce the risk of ARF in a high-risk surgical population. After obtaining approval of a local ethics committee and informed written consent of patients, a prospective, randomized, double-blinded trial was performed. Patients enrolled in the study were determined to be at high-risk for perioperative renal dysfunction and the primary end-point was defined as a >25% increase in creatinine. A total of 80 patients were enrolled who received either fenoldopam at 0.05 mcg/kg/minute or dopamine (control) at 2.5 mcg/kg/minute. Exclusion criteria included emergent surgery, preoperative dialysis, glaucoma and any allergy to fenoldopam or its infusion components. The 2 groups were similar with respect to clinical characteristics (age, sex, weight, diabetes, etc.) and intraoperative data (length of cardiopulmonary bypass (CPB), cross-clamp time, urinary output). No difference in outcome was observed between the two groups. ARF occurred in 17/40 (42.5%) of patients in the fenoldopam group and 16/40 (40%) in the dopamine group. Postoperative data with respect to peak serum creatinine, intensive care unit and hospital stay as well as mortality were also similar in the 2 groups. The investigators concluded that there was no benefit to the use of fenoldopam in decreasing the incidence of postoperative ARF in high risk cardiac surgical patients.

Comments: Postoperative ARF is unfortunately a known and potentially devastating complication of cardiac surgery. Thought to be related to extracorporeal circulation and its effects on renal physiology including altered blood flow (nonpulsatile), embolic insults and increases in circulating catecholamines and inflammatory mediators, multiple attempts have been made to identify prophylactic therapy that would reduce the incidence of ARF. However, no pharmacological agent has been proven to be clearly beneficial in reducing this complication.

Fenoldopam is a unique vasodilator that increases renal cortical and medullary blood flow while decreasing systemic vascular resistance. Its effects on renal blood flow has led to its increasing use as a prophylactic agent in cardiac catherization where IV dye is used, cardiac surgery and other surgical/medical situations where impaired renal function is seen. Previous studies involving fenoldopam were either not randomized/controlled, did not address high risk cardiac surgery patients, or had other limitations precluding them from being very definitive.

This study examined a cardiac surgery population at high risk for developing perioperative renal dysfunction. It was well designed as it was randomized, controlled and double-blinded with clear end-points. However, there were some limitations including:

The use of dopamine as a control. The debate regarding dopamine's value in this setting has been extensively discussed with most agreeing that there is no benefit to dopamine in preventing ARF. The authors state that despite this, it is still administered routinely in high-risk patients, and has not shown to be deleterious and therefore is a fair control.
No mention of the use of preoperative angiotensin converting enzyme inhibitors (ACE-I's). While there was no difference in the two groups with respect to use of diuretics, ACE-I's are frequently used in patients undergoing cardiac surgery and are thought to have renal protective benefits of their own. Perhaps fenoldopam used in conjunct with these agents (a sub-group) would have demonstrated some benefit.

The one significant difference in this study between the control (dopamine) group and the treatment (fenoldopam) group was the incidence of intraoperative hypotension, necessitating increased use of vasoconstrictive agents in the treatment group. In fact, the study was ended at the midway analysis point (originally scheduled to have 160 patients), as there was no benefit seen from fenoldopam and the significant increased incidence of hypotension during CPB with a trend towards increased use of vasoconstrictors led to the safety monitoring board ending the study early.

Cardiac surgery is known to have serious complications involving nearly every organ system. Postoperative ARF has been shown to be an independent predictor of increased mortality in cardiac surgery patients, demonstrating the importance of attempting to avoid this complication. This study demonstrates that in high-risk patients fenoldopam has no benefit in preventing ARF and may have actually induce hypotension necessitating the increased use of vasoconstrictor agents, with their own side effects. Given these results its routine use is not indicated, however it may have a role in select sub groups that were not delineated or examined in this study.

Table of Contents:

Literature Reviews