An urban ED at a tertiary level I trauma center conducted a retrospective observational review of patients from 2007 to 2013 who were administered flumazenil for known or suspected benzodiazepine overdose 7. In a review of 43 cases of flumazenil-related seizures reported to FDA, 42% occurred in patients who had also ingested tricyclic antidepressants 6. In their review of pediatric patients, only 1 patient was reported to have a seizure, and the medical toxicologist consulted on the case determined that the seizure was unrelated to the administration of flumazenil.Īlthough poison centers have an abundant database of toxicologic cases, reporting to poison centers is voluntary and does not capture all cases of overdoses and toxicity. Of the observed adult patients, 13 patients (1.4%) experienced seizures and 32% of patients were also exposed to a proconvulsant. Retrospective reviews conducted through the California Poison Control System from 1998 – 2008 looking at both pediatric and adult patients evaluated the safety of flumazenil use in benzodiazepine ingestions 4,5. tricyclic antidepressants, bupropion, etc.), those with benzodiazepine dependence, and those who have a benzodiazepine prescribed for seizure disorder. Patients who may be at risk for seizures are those who have also ingested a proconvulsant medication (i.e. The package insert of flumazenil contains a black box warning stating that the drug is associated with the occurrence of seizures, and states that providers should individualize the dosage and be prepared to manage seizures. Wakefulness may be transient and re-sedation can be observed due to its short clinical effect, however, this may be mitigated with the use of a continuous infusion. Reversal effects are typically seen within 1-2 minutes with a peak effect at 6-10 minutes 3. It is a competitive antagonist at these receptors and reverses the effects of benzodiazepines. Flumazenil is a 1,4-benzodiazepine derivative that has a high affinity for the benzodiazepine binding site on the GABA receptor. 2įlumazenil is a benzodiazepine receptor antagonist FDA approved in 1992 for reversal of benzodiazepine overdose and postoperative sedation from benzodiazepine anesthetics. Of those involving only benzodiazepines, 731 (1.25 %) patients experienced a major outcome and 11 (0.01 %) died. In 2019, there were 58,430 total benzodiazepine exposures reported to US poison centers. However, some patients with large benzodiazepine ingestions may benefit from flumazenil administration to avoid intubation. Most patients requiring intubation after benzodiazepine overdose have ingested multiple sedating substances. Overall the complication rate with benzodiazepine overdose is low 1. Intoxications with benzodiazepines are generally well-tolerated but can cause prolonged coma. Flumazenil associated seizures require treatment with alternative agents such as barbiturateīenzodiazepines are sedative-hypnotic drugs that cause central nervous system and respiratory depression.Adult patients should receive doses of 0.2 mg every 1-2 minutes until arousable.The risk of seizure following the administration of flumazenil in the literature is very low in appropriately selected patients.
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