Furthermore, innumerable cases of iatrogenic toxic oversedation in hospitals go unreported to the NPDS every year. Additional GABA-ergic toxicity cases involving non-benzodiazepine likely number in the thousands-per-year, too, but are not subcategorized by the American Association of Poison Control Centers’ Annual Report. The NPDS data almost certainly underestimate the total cases of sedative toxicity by a wide margin. In 2013, over 19,000 cases of benzodiazepine toxicity were reported through the National Poison Data System (NPDS) to have been treated in health care facilities, but during that same year the registry catalogued fewer than 1700 patients treated with flumazenil. This perspective has resulted in underutilization of the antidote. Therefore, the decision to use flumazenil in an unidentified poisoning may appear complex, where the benefits of rapid diagnosis and treatment seem offset by the possibility of significant adverse reactions. Īlthough flumazenil is of obvious benefit in a pure benzodiazepine poisoning, many toxic patients presenting to the emergency department suffer sedation potentiated by combinations of prescription medications, illicit drugs and/or alcohol. In those studies, patients who suffered such adverse reactions demonstrated clinical manifestations of multiple drug ingestions (most commonly involving tricyclic antidepressants), had previous histories of excessive benzodiazepine use, and/or were given flumazenil doses of at least 1 mg at a time. Although the drug is often associated with minor side effects such as salivation, vomiting and anxiety, only a few studies have been able to demonstrate significant adverse events such as seizures and cardiac arrhythmias. Flumazenil has been shown to work quickly and safely, serving as both a diagnostic and therapeutic tool. Iatrogenic and nosocomial complications may be minimized when wakefulness precludes the need for intubation, bladder catheterization, and other interventions, thus potentially reducing hospital lengths of stay.įlumazenil is an imidazole-benzodiazepine analog, which acts as a competitive antagonist of central benzodiazepine receptors on the GABA-A complex. This approach provides caregivers with means of obtaining a more accurate history of ingestion directly from the patient, as well as preventing some of the more severe complications of a comatose state, such as aspiration pneumonitis, airway obstruction, and respiratory depression. However, in cases of significant overdose resulting in drug-induced coma, an antidote can be used to reverse the effects of sedatives. Toxicity from benzodiazepines is rarely directly fatal. Oversedation, confusion, and prolonged intensive care stays are common complications. The sheer availability of these medications and other sedatives makes them frequently used agents in both intentional and unintentional poisoning. We conclude that flumazenil is a safe diagnostic and therapeutic antidote for cases of suspected sedative-hypnotic toxicity.īenzodiazepines are some of the most commonly prescribed sedative/hypnotic and anticonvulsant medications worldwide. No clinically significant adverse events occurred with flumazenil administration in patients who chronically used benzodiazepines or had a history of seizures. Comorbid anxiety disorders were associated with anxiety upon arousal, but no patient required medical intervention. Three patients experienced drooling, 7 experienced transient anxiety, and there were 2 separate episodes of odd behavior upon awakening from coma in a patient with personality disorder. In the prospective year, there were 12 instances of side effects out of 212 patients treated. There were no instances of arrhythmias or seizures. The overall positive response rate was over 80%. The following reports a six-year retrospective review of the practice and a one-year close observational study of bedside use of the antidote. A dose of 0.5 mg is given IV over 30 s, with repeat doses q1-2h as needed to sedated patients with relaxed autonomic indices and peripheral neurologic status. At one toxicology center, flumazenil is routinely employed in the emergency department and acute hospital setting. Although a direct antidote is available, it is rarely used due to fears of withdrawal and seizures. benzodiazepines) affects cognition, behavior, and functional status.
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