The Effect of Selective Intestinal Decontamination on the Hyperdynamic Circulatory State in Cirrhosis

A Randomized Trial

5 August 2003 | Volume 139 Issue 3 | Pages 186-193

Background: Peripheral vasodilatation is central to the pathogenesis of the accompanying hyperkinetic circulatory state and portal hypertension in cirrhotic patients. Selective intestinal decontamination with norfloxacin has been demonstrated to partially correct nitric oxide production in the forearm vasculature of cirrhotic patients.

Objective: To examine the effects of selective intestinal decontamination on regional and systemic hemodynamics in cirrhotic patients.

Design: Randomized, double-blind, placebo-controlled, crossover study.

Setting: Alfred Hospital, Melbourne, Australia.

Patients: 14 patients with alcohol-related cirrhosis and 14 matched healthy controls.

Intervention: Norfloxacin, 400 mg twice daily, for 4 weeks.

Measurements: Venous occlusion plethysmography was used to determine forearm blood flow. Cardiac output and the hepatic venous pressure gradient were determined after cardiac catheterization. Glomerular filtration rate was assessed by measuring inulin clearance. Serum levels of endotoxin were determined by chromogenic Limulus amebocytelysate assay.

Results: Norfloxacin significantly diminished serum endotoxin levels (average change, –2.14 EU/mL [95% CI, –3.6 to –0.68 EU/mL]). Derived systemic vascular resistance increased significantly with norfloxacin (2.94 units [CI, 0.74 to 5.11 units]) and was accompanied by an increase in mean arterial pressure (8.70 mm Hg [CI, 2.65 to 14.73]), a trend toward decreased cardiac output (–1.207 L/min [range, 0.05 to –2.37 L/min]), a decrease in forearm blood flow (–0.99 mL/100 mL per min [CI, –1.80 to –0.17 mL/100 mL per min]), and a trend toward reduced hepatic venous pressure gradient (–2.43 mm Hg [CI, –5.2 to 0.34 mm Hg]). Norfloxacin did not significantly alter glomerular filtration rate.

Conclusion: Selective intestinal decontamination with norfloxacin partially reverses the hyperdynamic circulatory state in cirrhotic patients without harming splanchnic or renal hemodynamics.

Editors' Notes Background Patients with advanced hepatic cirrhosis often experience a hyperdynamic circulatory state, possibly because nitric oxide is released by intestinal bacteria. Selective intestinal decontamination with norfloxacin may decrease nitric oxide release by altering the intestinal flora. Contribution This randomized, double-blind, placebo-controlled cross-over study shows that norfloxacin administration is associated with decreased serum endotoxin levels, attenuation of increased cardiac output, and maintenance of systemic vascular resistance in cirrhotic patients. Implications Norfloxacin may be useful in treating the hyperdynamic circulatory state in cirrhotic patients. Although the mechanism may not be explicitly proven by this study, it may involve a decrease in nitric oxide production. –The Editors

 

Author and Article Information

From Alfred Hospital and Baker Medical Research Institute, Prahran, Victoria, Australia.

Grant Support: By the Department of Gastroenterology and the Alfred and Baker Medical Unit, Alfred Hospital, Prahran, Victoria, Australia.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Jaye P.F. Chin-Dusting, PhD, Baker Medical Research Institute, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia; e-mail, j.chin{at}alfred.org.au.

Current Author Addresses: Drs. Rasaratnam and Dudley: Department of Gastroenterology, Alfred Hospital, Commercial Road, Melbourne 3004, Australia.

Drs. Kaye, Jennings, and Chin-Dusting: Alfred and Baker Medical Unit, Wynn Domain, Baker Medical Research Institute, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia.

Author Contributions: Conception and design: B. Rasaratnam, F. Dudley, J. Chin-Dusting.

Analysis and interpretation of the data: B. Rasaratnam, F. Dudley, J. Chin-Dusting.

Drafting of the article: B. Rasaratnam, F. Dudley, J. Chin-Dusting.

Critical revision of the article for important intellectual content: B. Rasaratnam, D. Kaye, G. Jennings, F. Dudley, J. Chin-Dusting.

Final approval of the article: B. Rasaratnam, D. Kaye, F. Dudley, J. Chin-Dusting.

Provision of study materials or patients: B. Rasaratnam, D. Kaye, G. Jennings, F. Dudley, J. Chin-Dusting.

Statistical expertise: J. Chin-Dusting.

Obtaining of funding: F. Dudley, J. Chin-Dusting.

Administrative, technical, or logistic support: B. Rasaratnam, D. Kaye, G. Jennings.

Collection and assembly of data: J. Chin-Dusting.