Li 2009

Methods	Double‐blind, single‐centre, parallel‐arm RCT.
Participants	72 participants with overt hepatic encephalopathy (Grade III or IV) associated with cirrhosis (65%) or fulminant hepatic failure (35%). Diagnostic criteria for participants with cirrhosis corresponded to acute hepatic encephalopathy. Mean age ± SD: flumazenil: 55.4 ± 6.6 years; placebo: 56.8 ± 7.9 years. Proportion of men: 63%. Aetiology of cirrhosis: not reported. Proportion testing positive for benzodiazepines at baseline (Table 7): apparently not performed (not specifically stated).
Interventions	Intervention comparison: slow intravenous injection flumazenil 0.5 mg followed by intravenous infusion of flumazenil 1 mg of over 30 minutes versus placebo (saline). Total dose of flumazenil: 1.5 mg. Cointerventions: lactulose enemas, L‐ornithine L‐aspartate
Outcomes	Outcomes included in meta‐analyses: mortality, hepatic encephalopathy (Table 3), and serious adverse events (Table 8) assessed after a maximum of 2 weeks.
Neuropsychiatric assessment	Baseline and post infusion: Clinical scale (not specified) assessed at baseline; Glasgow Coma Score (Table 4) assessed at baseline and after 2 hours; Electroencephalography assessed at baseline and after 2 hours.
Inclusion period (date)	May 2006 to July 2008.
Country	China.
Notes	Included data: the trial report did not provide separate information on participants with cirrhosis and participants with acute liver failure. Therefore, we conducted a sensitivity analysis excluding this trial.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported.
Allocation concealment (selection bias)	Low risk	Double‐blind administration of flumazenil and placebo.
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	Low risk	No missing outcome data and all participants included in the analyses.
Selective reporting (reporting bias)	Low risk	Trial described clinically relevant outcomes. We had no access to information about outcomes described in original protocol or information in trial registries.
For‐profit funding	Unclear risk	No information provided.
Other bias	Low risk	No other biases.
Overall assessment	High risk	High risk of bias.