 CLINICAL INVESTIGATIONS Anesthesiology 2004; 101:576 – 82 © 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Effects of Short-term Fenoldopam Infusion on Gastric Mucosal Blood Flow in Septic Shock Andrea Morelli, M.D.,* Monica Rocco, M.D.,* Giorgio Conti, M.D.,† Alessandra Orecchioni, M.D.,* Andrea De Gaetano, M.D., Ph.D. (Math),‡ Flaminia Coluzzi, M.D.,§ Enrico Vernaglione, M.D.,§ Paolo Pelaia, M.D., Paolo Pietropaoli, M.D.# Background: Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality. As result of splanchnic ischemia, mucosal permeability increases. Consider- ing the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity, dopamine-1 receptor stimulation could be helpful in septic shock. The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfu- sion in patients with septic shock. Furthermore, the authors tested the hypothesis that the addition of fenoldopam (0.1 g· kg 1 · min 1 ) to a combination of norepinephrine and dobut- amine (5 g · kg 1 · min 1 ) may improve gastric mucosal perfu- sion in septic shock. Methods: Patients with septic shock were randomized to a double-blind 2-h infusion of fenoldopam (n  20) or placebo (n  20). Each group received dobutamine (5 g · kg 1 · min 1 ), and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg. A laser- Doppler probe and tonometer were introduced into the gastric lumen. Results: A significant increase in gastric mucosal perfusion, detected by laser-Doppler flowmetry, was observed in the group treated with fenoldopam (P < 0.05). In addition, this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged. Differences in gastroarte- rial partial pressure of carbon dioxide values were not statisti- cally significant in the fenoldopam and placebo groups. Conclusions: The study showed that, for the same mean arte- rial pressure, short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock. SEPTIC shock is characterized by decreased peripheral vascular resistance, impaired distribution of blood flow, and oxygen extraction with normal or improved oxygen delivery. Altered peripheral resistance in septic shock results in redistribution of cardiac output (CO) with hypoperfusion of splanchnic organs. The gut mucosa has been identified as one of the most important targets of injury during septic shock. An alteration of blood flow within the gut wall may be one contributing factor to gut mucosal injury. Gut mucosal hypoxia may play a key role in the pathogenesis of multiple organ disfunction. 1,2 The combination of vasodilatation and pronounced vascular hyporeactivity often necessitates a treatment with high- dose norepinephrine to maintain blood pressure and to increase oxygen delivery in septic shock. However, the administration of high-dose norepinephrine may cause or at least worsen splanchnic hypoperfusion. 3,4 To prevent gut ischemia and to improve gut perfusion, numerous gut- directed therapeutic approaches have been attempted by administration of vasoactive drugs. 5–7 Unfortunately, the lack of splanchnic selectivity by these vasoactive agents could yield adverse effects on gut perfusion and oxygen- ation. Fenoldopam is a relatively selective postsynaptic do- pamine (DA)-1 receptor agonist, with weak 5-hydroxytryp- tamine-2 receptor agonist activity and no significant affinity for , , or DA-2 receptors. 8 As shown in the studies by Guzman et al., 9,10 during hemorrhage, fenoldopam re- stored portal vein flow to near baseline, maintained frac- tional splanchnic blood flow, and mitigated the increase in ileal mucosal partial pressure of carbon dioxide (PCO 2 ). In addition, fenoldopam redistributed blood flow away from the serosal to the mucosal layer, both at baseline and during hemorrhage. Considering that few validated techniques to measure gastric perfusion can be applied to humans, available data on the effects of fenoldopam on gut circulation in patients with septic shock are limited. The goal of this study is to evaluate the effects of low-dose fenoldopam infusion (0.1 g · kg -1 · min -1 ) on gastric mucosal perfu- sion (GMP) using laser-Doppler flowmetry and on intramu- cosal pH using gastric tonometry in patients with septic shock treated with a combination of norepinephrine (perfused at rates achieving mean arterial pressure [MAP] between 70 and 80 mmHg) and dobutamine (5 g · kg -1 · min -1 ). Materials and Methods Patients The study protocol was approved by the local institu- tional ethics committee (University of Rome “La Sapi- enza,” Rome, Italy). Informed written consent was ob- tained from the closest relative of each patient. The study was performed in two different multidisci- plinary intensive care units (ICUs) in a university hospi- tal. Forty critically ill patients were enrolled in the study * Assistant Professor, § Resident, # Full Professor and Head, Department of Anesthesiology and Intensive Care, University of Rome “ La Sapienza.” † Asso- ciate Professor, Department of Anesthesiology and Intensive Care, Catholic University of Rome, Rome, Italy. ‡ National Council of Research, Institute of Systems Analysis and Computer Science, Biomath Lab, Rome, Italy.  Full Pro- fessor and Head, Department of Anesthesiology and Intensive Care, University of Ancona, Ancona, Italy. Received from the Department of Anesthesiology and Intensive Care, Univer- sity of Rome “ La Sapienza,” Rome, Italy. Submitted for publication May 8, 2003. Accepted for publication August 11, 2003. Supported by an independent re- search grant from the Department of Anesthesiology and Intensive Care, Univer- sity of Rome “ La Sapienza.” Address reprint requests to Dr. Morelli: Via B. Oriani 2, 00197 Rome, Italy. Address electronic mail to: andrea.morelli@uniroma1.it. Individual article re- prints may be purchased through the Journal Web site, www.anesthesiology.org. Anesthesiology, V 101, No 3, Sep 2004 576 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/101/3/576/356068/0000542-200409000-00005.pdf by guest on 15 January 2023