The Effect of Fenoldopam and Dopexamine on Cytokine and Endotoxin Release following On-Pump Coronary Artery Bypass Grafting: A Prospective Randomized Double-Blind Trial

Abstract

Surgical trauma, exposure to an external circuit, and reduced organ perfusion contribute to the systemic inflammatory response following cardiopulmonary bypass (CPB). Reduced splanchnic perfusion causes disruption of the gastrointestinal mucosal barrier and the release of endotoxins. Fenoldopam (a new dopamine 1 receptor agonist) has been shown to be a specific renosplanchnic vasodilator in animal and human studies. We studied the effects of fenoldopam on the systemic inflammatory response and the release of endotoxins after CPB and compared the results with those for dopexamine. Our prospective randomized study included 42 consecutive patients with good to moderate left ventricular function who were to undergo elective or inpatient coronary artery bypass grafting. We used closed envelope method to randomize patients to receive 0.2 μg/kg per minute of fenoldopam (n = 14), 2 μg/kg per minute of dopexamine (n = 14), or normal saline (n = 14). Patients received their respective treatments continuously from anesthesia induction until the end of the first 24 postoperative hours. Interleukin 1β (IL-1β), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α, complement 3a (C3a), C4a, C5a, and endotoxins were measured during the perioperative period. Repeated-measures analysis of variance was used to evaluate the results for the timed samples. There were no statistical differences between the groups with respect to pre- and intraoperative variables. Release of C3a was attenuated in the fenoldopam group (P = .002), and release of IL-6 and IL-8 was attenuated in the postoperative period in the fenoldopam group (P = .012 and .015, respectively). The other interleukins showed no uniform release in any of the 3 groups. There were no statistically significant differences in serum endotoxin elevation between the 3 groups. A partial attenuation in the inflammatory response is possible with fenoldopam infusion. The elevation in serum endotoxin levels was not affected by dopexamine or fenoldopam infusion.