Table 6.

Serious adverse events

Trial	Number of participants	Included in analyses of serious adverse events	Data included in primary analysis	Serious adverse events
Amodio 1997	13	No	Cross‐over RCT. Data from the first treatment period not described.	Publication does not describe any deaths or other serious adverse events.
Barbaro 1998	527	Yes	Cross‐over RCT. Data from the first treatment period included.	Thirteen non‐responders in the flumazenil group and 17 non responders in the placebo group died 3 to 4 days (range 2‐6) after randomisation. The causes of dead were septic shock (20 participants); hypovolaemic shock (8 participants) and lactic acidosis (2 participants) but information was not provided on the number of deaths by cause in each group.
Cadranel 1995	14	Yes	Cross‐over RCT. Data from the first treatment period included.	One of 12 responders died from septic shock on day 4 and 2 of 6 non‐responders died from septic shock (day 2) and lactic acidosis (day 4) but information is not provided on the groups to which they a were allocated.
Dursun 2003	40	Yes	Parallel‐arm RCT. We included all participants in the analyses.	Publication did not describe any deaths or other serious adverse events.
Giger‐Mateeva 1999	10	No	Cross‐over RCT. Data from the first treatment period not described.	Publication did not describe any deaths or other serious adverse events.
Gooday 1995	10	Yes	Cross‐over RCT. Data from the first treatment period included.	Publication did not describe any deaths or other serious adverse events.
Gyr 1996	49	Yes	Parallel‐arm RCT. We included all participants in the analyses.	Four of 28 participants allocated to flumazenil and 5 of 21 allocated to placebo died within 4 weeks of the trial. One participant in the placebo group died with respiratory failure during the course of the study. The authors described participants as having severe liver disease suggesting that the cause of death in the remaining 8 participants may have been cirrhosis‐related although this is not specifically stated. The investigators classified the remaining adverse events viz flushing, nausea, vomiting, and irritability, which were experienced by 4 participants, as non‐serious.
Hermant 1991	12	Yes	Parallel‐arm RCT. We included all participants in the analyses.	Publication did not describe any deaths or other serious adverse events.
Klotz 1989	2	No	Cross‐over RCT. Data from the first treatment period were not described.	Publication does not describe any deaths or other serious adverse events.
Lacetti 2000	54	Yes	Parallel‐arm RCT. We include all participants in the analyses.	Six of 28 participants in the flumazenil group and 5 of 26 in the control group died. The causes of death were not provided.
Li 2009	72	Yes	Parallel‐arm RCT. The included participants had hepatic encephalopathy associated with cirrhosis or acute liver failure. Data were not provide separately for the 2 groups.	Five of 39 participants in the flumazenil group and 4 of 33 participants in the control group died. The causes of death were not provided.
Pomier‐Layrargues 1994	21	Yes	Cross‐over RCT. Data from the first treatment period were included.	Publication did not describe any deaths or other serious adverse events.
Van der Rijt 1995	18	Yes	Cross‐over RCT. The included participants had hepatic encephalopathy associated with cirrhosis or acute liver failure. Data were not provide separately for the 2 groups.Data from the first treatment period were included.	Publication did not describe any deaths or other serious adverse events. Two participants with fulminant hepatic failure underwent orthotopic liver transplantation on day one of the study
Zhu 1998	25	Yes	Parallel‐arm RCT. We included all participants in the analyses.	Three of 13 participants in the flumazenil group and 5 of 12 participants in the control group died. The causes of death were not provided

RCT: randomised clinical trial.