The efficacy of flumazenil in subclinical to mild hepatic encephalopathic ambulatory patients. A prospective, randomised, double-blind, placebo-controlled study.
OBJECTIVE
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with fulminant hepatic failure and chronic liver disease. Its pathogenesis is unclear. One of the factors implicated is enhanced GABA-ergic tone, which is probably related to increased concentrations of cerebral benzodiazepine (BNZ). In the present study, we tested flumazenil, a cerebral BNZ antagonist, in cirrhosis patients with hepatic encephalopathy.


METHODS
Out of 47 patients, 7 were excluded prior to randomization for various reasons. Twenty patients were included in the flumazenil group and 20 in the placebo group in a prospective, randomized, double-blind, placebo-controlled study. Patients were given flumazenil (1 mg/h, continuous IV infusion) or an equal volume of saline solution for 5 hours. Before and after treatment, portosystemic encephalopathy (PSE) stage and number connection test (NCT) scores were checked every half hour for 5 hours. EEG was recorded 15 minutes before and 1 hour after treatment.


RESULTS
While significant improvements were determined in PSE stage and NCT score in the flumazenil group, there were no such improvements in the placebo group. There was no statistically significant difference between pre- and post-treatment EEGs in either group.


CONCLUSIONS
It was concluded that continuous IV infusion of flumazenil had beneficial and safe effects in the treatment of hepatic encephalopathy patients.
Dursun
Mehmet
M
Dicle University Hospital, Diyarbakir, Turkey. dursunm@dicle.edu.tr
Caliskan
Mustafa
M
Canoruc
Fikri
F
Aluclu
Ufuk
U
Canoruc
Naime
N
Tuzcu
Alpaslan
A
Yilmaz
Serif
S
Isikdogan
Abdurrahman
A
Ertem
Meliksah
M
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000627:therapeutic use*; D018757:GABA Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D018757:GABA Modulators; D005442:Flumazenil