Klotz 1989

Methods	Double‐blind, cross‐over, single‐centre, placebo‐controlled RCT.
Participants	2 participants with cirrhosis and stable hepatic encephalopathy (Grade III). Description corresponded to chronic overt hepatic encephalopathy although this was not specifically stated. Proportion of men: not reported. Mean age: not reported. Aetiology of liver disease: alcohol 100%. Proportion testing positive for benzodiazepines at baseline (Table 7): apparently not performed (not specifically stated).
Interventions	Intervention comparison: intravenous infusion flumazenil 1 mg over 1 minute versus placebo. Total dose of flumazenil: 1 mg. Washout period: not specified. Cointerventions: not reported.
Outcomes	Outcomes included in meta‐analyses: mortality and serious adverse events (Table 8) assessed for a maximum of 2 hours post interventions.
Neuropsychiatric assessment	Clinical assessment of mental status: assessed after 2 hours (no specific score; timing not specified).
Inclusion period (date)	Not described.
Country	Germany.
Notes	Included data: investigators described the design as cross‐over but did not provide data from the first intervention period. Therefore, we were unable to include the trial in our analyses.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Trial described as double blind and placebo controlled. However, trial only reported as a letter and the type of placebo (or mode of administration) is not described.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Trial described as double blind and placebo controlled. However, trial only reported as a letter and the type of placebo (or mode of administration) is not clearly described.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data and all participants included in analyses.
Selective reporting (reporting bias)	Low risk	Trial gave impression that participants survived although this was not specifically stated. We had no access to information about outcomes described in the original protocol or information in trial registries.
For‐profit funding	Unclear risk	No information provided.
Other bias	High risk	Trial only included 2 participants.
Overall assessment	High risk	High risk of bias.