EFFECT OF FLUMAZENIL ON THE ELECTROENCEPHALOGRAM OF PATIENTS WITH PORTOSYSTEMIC ENCEPHALOPATHY - RESULTS OF A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER TRIAL
M. Groeneweg et al., EFFECT OF FLUMAZENIL ON THE ELECTROENCEPHALOGRAM OF PATIENTS WITH PORTOSYSTEMIC ENCEPHALOPATHY - RESULTS OF A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER TRIAL, Electroencephalography and clinical neurophysiology, 98(1), 1996, pp. 29-34
The efficacy of the benzodiazepine antagonist flumazenil has been asse
ssed clinically in a double blind, randomised, placebo-controlled mult
icentre study in patients with grade I-III portosystemic encephalopath
y. In an ancillary study reported here the effect of flumazenil on the
electroencephalogram (EEG) was analysed in 32 patients who had EEG gr
ading according to protocol. Following the baseline observation period
, patients were randomised to receive (at 1 min interval) 3 sequential
bolus injections of flumazenil (0.4, 0.8 and 1 mg) or placebo followe
d by infusions of flumazenil (1 mg/h) or placebo for 3 h. Patients wer
e monitored for 5 h after infusion. A positive response was defined as
1 point improvement in EEG grade. After independent analysis of the E
EG gradings 5 out of 17 (29%) flumazenil treated patients showed an im
provement in EEG grading (3 after bolus, 2 during follow-up) compared
to 2 out of 15 (13%) placebo treated patients (1 after bolus, 1 during
follow-up) (95% confidence interval of difference: -12% to +50%). Of
the 5 EEG responders after flumazenil, 3 also had an improvement in cl
inical PSE grading (none after bolus, 2 during infusion, 1 during foll
ow-up), compared to neither of the 2 EEG responders after placebo. EEG
responders did not differ from non-responders with respect to Child-P
ugh score, basal EEG, PSE grade and positivity for benzodiazepines. In
conclusion, treatment perspectives for flumazenil in portosystemic en
cephalopathy appear to be present for only a minority of patients; how
ever, this study yields no support for a major role of benzodiazepine
antagonists in the treatment of hepatic encephalopathy.