Norfloxacin therapy for hepatopulmonary syndrome: a pilot randomized controlled trial.
OBJECTIVE
The hepatopulmonary syndrome occurs in up to one-third of patients with cirrhosis. Animal models of this disease suggest that endotoxemia might cause nitric oxide-mediated vascular dilatation that can be inhibited by the antibiotic norfloxacin. We sought to test this hypothesis in humans.


METHODS
We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg twice daily for 4 weeks with a 4-week washout period to assess the feasibility of a larger trial. The primary clinical end point was change in alveolar-arterial oxygen gradient (AaDO₂).


RESULTS
Recruitment was challenging, and change in AaDO₂ was highly variable. We recruited 9 adults (1 woman; age, 60 ± 9 years; AaDO₂, 50 ± 22 mm Hg). AaDO₂ decreased by 0.8 ± 4.8 and 3.4 ± 12.4 mm Hg while on norfloxacin and placebo, respectively (P = .59).


CONCLUSIONS
Recruitment difficulties and variability of the primary outcome measure suggest the need for a multicenter clinical research network for future therapeutic trials in this disease. There was no major effect of norfloxacin on gas exchange in patients with hepatopulmonary syndrome.
Gupta
Samir
S
Department of Medicine, University of Toronto, Ontario, Canada. guptas@smh.toronto.on.ca
Faughnan
Marie E
ME
Lilly
Les
L
Hutchison
Stuart
S
Fowler
Robert
R
Bayoumi
Ahmed M
AM
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005260:Female; D020065:Hepatopulmonary Syndrome / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009643:Norfloxacin / Q000008:administration & dosage*; D010865:Pilot Projects; D011659:Pulmonary Gas Exchange; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D009643:Norfloxacin