Unintentional drug overdoses killed 4,390 people in UK in 2021, 33% after use of potent benzodiazepines (benzodiazepines; eg. etizolam, alprazolam) alone or in combination with opioids, gabapentinoids (e.g. gabapentin), and/or cocaine [1, 2]. Pre-hospital intramuscular (an injection into a person’s muscle) use of the opioid antidote naloxone has been introduced by the government and is effective at preventing opioid deaths. The equivalent benzodiazepine antidote (flumazenil) is not used pre-hospital, in part because of a perceived risk of causing seizures [3]. However, a recent meta-analysis suggested this risk is low (<1%) [4]. We surveyed Emergency Physicians (n=124) who considered a low rate of seizures (<1%) to be acceptable if flumazenil reverses BZD-induced respiratory depression and is proven in future to prevent deaths [see bit.ly/3LD0J5X]. Given the surge in deaths associated with benzodiazepines, there is an urgent need to determine whether intramuscular flumazenil is safe and effective, with the ultimate objective of using it to prevent out-of-hospital deaths from unintentional mixed drug overdoses involving benzodiazepines.
Intravenous flumazenil is available for BZD and mixed opioid/BZD overdose, but little used because of a potential risk of causing seizures in patients who have co-ingested epileptogenic medicines. However, the evidence for significant harm from such use of flumazenil is modest. A recent systematic review summarised the evidence on efficacy and safety of flumazenil, in which both animal and human studies suggested it rarely causes seizures in patients [5]. The overall evidence was that intramuscular flumazenil may be safe but further research is required to determine if it is safe and effective in populations with high levels of benzodiazepine use, who are likely also dependent.