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. 2017 Aug 10;2017(8):CD002798. doi: 10.1002/14651858.CD002798.pub4

Zhu 1998.

Methods Double‐blind, single‐centre, parallel‐arm, placebo‐controlled RCT.
Participants 25 participants with cirrhosis and overt hepatic encephalopathy (Grade II to IV). Precipitating factors are described (Table 5).
Mean age ± SD: flumazenil: 62.2 ± 2.7 years; placebo: 52.2 ± 3.3 years.
Proportion of men: 69%.
Aetiology of cirrhosis: alcohol 80%; hepatitis B/C 12%.
Proportion testing positive for benzodiazepines at baseline (Table 6): not conducted (not specifically stated).
Interventions Intervention comparison: intravenous infusion flumazenil 1 mg over 5 minutes versus placebo (saline).
Total dose of flumazenil: 1 mg.
Cointerventions: intravenous branched‐chain amino acids.
Outcomes Outcomes included in meta‐analyses: mortality, hepatic encephalopathy (Table 2), and serious adverse events (Table 7) assessed for a maximum of 2 weeks (until death or discharge).
Neuropsychiatric assessment Baseline and post infusion:
  • Clinical assessment of hepatic encephalopathy (Table 3).

Inclusion period (date) April 1995 to March 1996.
Country China.
Notes Included data: all participants were included in the analyses.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Random numbers with stratified block randomisation.
Allocation concealment (selection bias) Low risk Administration of concealed drug containers with sealed, opaque, serially numbered envelopes.
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Blinding of participants and personnel.
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Blinding of outcome assessment.
Incomplete outcome data (attrition bias) 
 All outcomes Unclear risk Missing outcome data not described.
Selective reporting (reporting bias) Low risk Trial described clinically relevant outcomes. We had no access to information about outcomes described in the original protocol or information in trial registries.
For‐profit funding High risk Roche supplied the flumazenil.
Other bias Low risk No other biases.
Overall assessment High risk High risk of bias.

RCT: randomised clinical trial; SD: standard deviation.