Respiratory compromise occurs in less than 10% of pediatric cases, and hypotension has not been reported.īenzodiazepine overdose is usually suspected or diagnosed based on clinical presentation. Ataxia is the most common sign of toxicity in children, occurring in 90% of pediatric patients. In children with benzodiazepine toxicity, most will have symptoms within four hours of ingestion. Iatrogenic causes of toxicity can be seen when benzodiazepines are combined with other drugs during procedural sedation, particularly with opiates such as fentanyl. Life-threatening respiratory depression can be seen with large oral ingestions with or without coingestants. Respiratory depression or compromise, while less common when compared to barbiturates, is the most important adverse effect requiring immediate intervention. Cardiac-related effects and fatalities are rare in pure benzodiazepine toxicities. The classic presentation of an isolated benzodiazepine overdose consists of CNS depression with normal vital signs. Patients with benzodiazepine toxicity will primarily present with central nervous system depression ranging from mild drowsiness to a coma-like, stuporous state. While propylene glycol toxicity is rare, it must be considered when patients are receiving large or continuous infusions of parenteral benzodiazepines, for example, when treating severe sedative or ethanol withdrawal syndromes such as delirium tremens.
DIAZEPAM ANTIDOTE SKIN
Propylene glycol is the diluent used in the parenteral formulations for these two benzodiazepines, and prolonged use can cause propylene glycol toxicity, which includes skin and soft tissue necrosis, hemolysis, cardiac dysrhythmias, hypotension, significant lactic acidosis, seizure, and multisystem organ failure. Patients with severe toxicity will present in a stuporous or comatose state, and immediate airway management and mechanical ventilation may be required.Ī unique toxidrome related to parenteral formulations of diazepam and lorazepam is propylene glycol poisoning. The dose required to produce respiratory compromise is difficult to quantify and depends on multiple factors, including dosage, tolerance, weight, age, coingestants, and even genetics. Respiratory compromise is uncommon in isolated benzodiazepine ingestions, but if taken with coingestants such as ethanol or other drugs/medications, respiratory depression can be noted. It is important to note that most intentional ingestions of benzodiazepines do involve coingestants, the most common being ethanol, leading to substantial respiratory depression and airway compromise. Classic symptoms include slurred speech, ataxia, and altered mental status. Many patients will still be arousable and even provide a reliable history. The classic presentation in patients with isolated benzodiazepine overdose will include central nervous system (CNS) depression with normal or near-normal vital signs. īenzodiazepines taken in toxic doses without other coingestants rarely cause a significant toxidrome. The low incidence of respiratory depression with benzodiazepines, which differentiates it from barbiturates, is related to the low density of binding sites in the brainstem, which houses the respiratory center. This binding ultimately increases the flow of chloride ions through the GABA ion channel, causing postsynaptic hyperpolarization, which decreases the ability to generate an action potential. Benzodiazepines do not alter the production, release, or metabolism of GABA but instead potentiates its inhibitory actions by augmenting or enhancing receptor binding. Benzodiazepines bind at the interface of the GABA-A receptor and subsequently lock the receptor into a configuration that increases its affinity for GABA. The GABA-A receptor, depending on various arrangements of its subunits, determines its affinity for various agents that bind to the receptor. Benzodiazepines exert their effect via modulation of the gamma-aminobutyric acid A (GABA-A) receptor, the primary inhibitory neurotransmitter in the central nervous system. Benzodiazepines are organic bases with a benzene ring and a 7-member diazepine moiety, with variable side chains that determine the potency, duration of action, metabolite activity, and rate of elimination.
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