The Effect of Fenoldopam and Dopexamine on Cytokine and Endotoxin Release following On-Pump Coronary Artery Bypass Grafting: A Prospective Randomized Double-Blind Trial
Background: 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.
Methods: 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 ?g/kg per minute of fenoldopam (n = 14), 2 ?g/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 1? (IL-1?), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor ?, 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.
Results: 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.
Conclusion: 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.
Adluri RKP, Singh AV, Skoyles J, et al. 2009. The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic function following coronary artery bypass grafting with hypothermic cardiopulmonary bypass. Eur J Cardiothorac Surg 35:988-94.nBach F, Grundmann U, Baeur M, et al. 2002. Modulation of the inflammatory response to cardiopulmonary bypass by dopexamine and epidural anesthesia. Acta Anaesthesiol Scand 46:1227-35.nBerendes E, Möllhoff T, Van Aken H, et al. 1997. Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. Anesth Analg 84:950-7.nBrodgen RN, Markham A. 1997. Fenoldopam: a review of its pharmacodynamic and pharmacokinetic properties and intravenous clinical potential in the management of hypertensive urgencies and emergencies. Drugs 54:634-50.nChenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. 1981. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 304:497-503.nCremer J, Martin M, Redl H, et al. 1996. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 61:1714-20.nElgebaly SA, Houser SL, el Kerm AF, Doyle K, Gillies C, Dalecki K. 1994. Evidence of cardiac inflammation after heart operations. Ann Thorac Surg 57:391-6.nGombotz H, Plaza J, Mahla E, Berger J, Metzler H. 1998. DA1-receptor stimulation by fenoldopam in the treatment of post cardiac surgical hypertension. Acta Anaesthesiol Scand 42:834-40.nHalpenny M, Laksmi S, O'Donnell A, O'Callaghan-Enright S, Shorten GD. 2001. Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting. Anaesthesia 56:953-60.nJansen NJ, van Oeveren W, Gu YJ, van Vliet MH, Eijsman L, Wildevuur CR. 1992. Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass. Ann Thorac Surg 54:744-8.nKirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. 1983. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 86:845-57.nLisbon A. 2003. Dopexamine, dobutamine, and dopamine increase splanchnic blood flow: what is the evidence? Chest 123(suppl):460S-3S.nMathur VS, Swan SK, Lambrecht LJ, et al. 1999. The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects. Crit Care Med 27:1832-7.nMorelli A, Rocco M, Conti G, et al. 2004. Effects of short-term fenoldopam infusion on gastric mucosal blood flow in septic shock. Anesthesiology 101:576-82.nNilsson L, Kulander L, Nyström SO, Eriksson O. 1990. Endotoxins in cardiopulmonary bypass. J Thorac Cardiovasc Surg 100:777-80.nOhri SK, Bjarnason I, Pathi V, et al. 1993. Cardiopulmonary bypass impairs small intestinal transport and increase gut permeability. Ann Thorac Surg 55:1080-6.nRiddington DW, Venkatesh B, Boivin CM, et al. 1996. Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. JAMA 275:1007-12.nRocke DA, Gaffin SL, Wells MT, Keon Y, Brock-Utine JG. 1987. Endotoxemia associated with cardiopulmonary bypass. J Thorac Cardiovasc Surg 93:832-7.nSchwarte LA, Picker O, Schindler AW, Fournell A, Scheeren TW. 2003. Fenoldopam—but not dopamine—selectively increases gastric mucosal oxygenation in dogs. Crit Care Med 31:1999-2005.nSharpe DAC, Mitchel IM, Kay EA, McGoldrick JP, Munsch CM, Kay PH. 1999. Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine and dopexamine. Perfusion 14:29-36.nTao W, Zwischenberger JB, Nguyen, et al. 1995. Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand. J Thorac Cardiovasc Surg 110:819-28.nTaylor KM, Bain WH, Jones JV, Walker MS. 1976. The effect of hemodilution on plasma levels of cortisol and free cortisol. J Thorac Cardiovasc Surg 72:57-61.nUtley JR. 1990. Pathophysiology of cardiopulmonary bypass: current issues. J Card Surg 5:177-89.nWan S, LeClerc JL, Vincent JL. 1997. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 112:676-92.nWan S, Marchant A, DeSmet JM, et al. 1996. Human cytokine response to cardiac transplantation and coronary artery bypass grafting. J Thorac Cardiovasc Surg 111:469-77.n