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Dopexamine reduces the incidence of acute inflammation in the gut mucosa after abdominal surgery in high-risk patients

Byers, Richard J. MRCPath; Eddleston, Jane M. FRCAnaes; Pearson, Robert C. MD, FRCS; Bigley, Graham AIBMS; McMahon, Ray F. T. MD, FRCPath

Clinical Investigations

Objective: To evaluate the effect of dopexamine on the incidence of acute inflammation in the stomach/duodenum in patients undergoing abdominal surgery ≥1.5 hrs with a minimum of one high-risk criterion.

Design: Prospective, randomized, double-blind, placebo-controlled study. This study was conducted as a side arm to a multicenter, multinational study.

Setting: University hospital in an adult intensive care unit.

Patients: Thirty-eight patients.

Interventions: Patients were stabilized with fluid, blood products, and supplementary oxygen to achieve predetermined goals: cardiac index > 2.5 L/min/m2, mean arterial blood pressure of 70 mm Hg, pulmonary arterial occlusion pressure of 10 mm Hg, hemoglobin of 100 g/L, and arterial saturation of 94%. After stabilization, the study drug (either placebo [group A], dopexamine 0.5 μg/kg/min [group B], or dopexamine 2.0 μg/kg/min [group C]) was commenced. The study drug infusion was started 2 to 12 hrs before surgery and infused for 24 hrs after surgery. Estimation of upper gut blood flow was assessed using a gastric tonometer, and gastroscopy with biopsy was performed before surgery (after induction of anesthesia) and 72 hrs after surgery. Comparisons were made between endoscopic findings and histologic proof of acute inflammatory changes. In addition, biopsies were assessed for the presence in the mucosa of mast cells, myeloperoxidase activity, and inducible nitric oxide synthase.

Measurements and Main Results: Intramucosal pH decreased significantly with time in all three groups (p < .001), reaching the lowest point at the end of surgery. There was no difference among the groups. Endoscopy visualized acute inflammatory changes in 58.3% of group A patients, 46.2% of group B patients, and 53.9% of group C patients after hemodynamic optimization. At 72 hrs, dopexamine-treated patients compared with placebo-treated patients had a significantly lower incidence of gastric and duodenal acute inflammatory changes, as defined by myeloperoxidase activity (37.5% in groups B and C vs. 86% in group A; p < .05).

Conclusion: Dopexamine in doses of 0.5 and 2.0 μg/kg/min affords significant histologic protection to the upper gastrointestinal tract mucosa 72 hrs after operation in high-risk surgical patients undergoing abdominal surgery.

From the Department of Pathological Sciences, University of Manchester (Drs. Byers and McMahon and Mr. Bigley); and the Departments of Critical Care Medicine (Dr. Eddleston) and Surgery (Dr. Pearson), Critical Care Unit, Manchester Royal Infirmary, Manchester, United Kingdom.

Address requests for reprints to: Dr. J. M. Eddleston, Critical Care Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.

© 1999 Lippincott Williams & Wilkins, Inc.