James R. Emergency Medicine News: April 2016 - Volume 38 - Issue 4 - p 10–12
doi: 10.1097/01.EEM.0000482472.97837.98
"Flumazenil, when it was first introduced more than 25 years ago, promised to be an effective and safe antidote for any patient who might have benzodiazepine (BZD) toxicity. It was hyped to be like naloxone, a complete and excellent reversal agent with no downsides, even if BZDs were not contributing to the overdose. Flumazenil is a complete antidote in that it will immediately reverse all BZD effects, but its empiric use has not gained wide popularity for a number of reasons.
This antidote essentially has minimal upsides and some substantial downsides. Individuals who are truly BZD-addicted can suffer immediate BZD withdrawal from flumazenil use. BZD withdrawal is not usually life-threatening, but it can be associated with undesirable side effects and rarely seizures. Flumazenil can cause seizures in patients who have ingested seizurogenic drugs, the poster child being tricyclic antidepressants, so the universal empiric use of flumazenil as part of the so-called coma cocktail has been discouraged. BZD intoxication is generally well tolerated, even in large doses, but it can cause prolonged coma and respiratory depression, particularly when mixed with other sedative hypnotics and alcohol. Still, the empiric use of flumazenil in unknown overdoses and comatose patients has limited applicability..."