The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial.
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.


METHODS
Randomized, double-blind, placebo-controlled, crossover study.


METHODS
Alfred Hospital, Melbourne, Australia.


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


METHODS
Norfloxacin, 400 mg twice daily, for 4 weeks.


METHODS
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.


CONCLUSIONS
Selective intestinal decontamination with norfloxacin partially reverses the hyperdynamic circulatory state in cirrhotic patients without harming splanchnic or renal hemodynamics.
Rasaratnam
Brindhesha
B
Alfred Hospital and Baker Medical Research Institute, Prahran, Victoria, Australia.
Kaye
David
D
Jennings
Garry
G
Dudley
Francis
F
Chin-Dusting
Jaye
J
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D018988:Bacterial Translocation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004731:Endotoxins / Q000097:blood; D005542:Forearm / Q000098:blood supply; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009643:Norfloxacin / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D004731:Endotoxins; D009569:Nitric Oxide; D009643:Norfloxacin