Approach Considerations
The only available antidote-like drug is flumazenil for benzodiazepine intoxication. Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient. [9] All other therapy is supportive or designed to limit absorption or enhance elimination. Given that the major issues in an overdose are aspiration, respiratory depression or failure, hypoxia, hypotension, and cardiac arrhythmias, the most important aspects in managing an overdose situation are, as usual, the ABCs—airway, breathing, and circulation.
Prior to arrival in the emergency department obtain IV access, provide oxygen, and perform aggressive supportive care with airway protection as necessary. Ensure adequate airway and ventilation. Consider and reassess the need for endotracheal intubation. Ipecac syrup is not recommended for home use because of the fear of emesis after onset of respiratory depression.
Emergency Department Care
Gastric lavage may be performed if the patient presents obtunded within 1 hour of ingestion or rapidly deteriorates while in the emergency department. The airway should be secured in such instances prior to gastric intubation and lavage.
The use of activated charcoal has come under debate, and its liberal use is discouraged. In general, measures to prevent absorption (eg, emesis, gastric lavage) or increase excretion (eg, diuresis, catharsis) of ingested drugs have not been shown consistently to reduce mortality associated with drug toxicity. Considerable morbidity is associated with charcoal aspiration. Its use should be limited to substances that would be well absorbed and have a high likelihood of toxic dose ingestion. It is not recommended in instances in which GHB or GBL are known to be the only intoxicants.
Multi-dose activated charcoal (20-50 g q4h) is recommended for overdoses with barbiturates, glutethimide, and meprobamate.
Alkaline diuresis enhances elimination of phenobarbital and other long-acting barbiturates. It is recommended for all symptomatic patients with long-acting barbiturate toxicity. Consider hemodialysis or hemoperfusion in glutethimide, methyprylon, phenobarbital, meprobamate, and chloral hydrate poisoning.
Patients who have made a suicide attempt should be evaluated by a psychiatrist after the intoxication has resolved to determine if they need inpatient psychiatric care.
With barbiturate toxicity, patients may be discharged after 6 hours of observation, provided that they are asymptomatic or minimally symptomatic. Patients with glutethimide (Doriden) toxicity require 24 hours of observation in the hospital.
Flumazenil Therarpy
Benzodiazepines promote the binding of GABA to its receptor. The z-drugs (zopiclone, zaleplon and zolpidem) act in a similar manner. Flumazenil is a benzodiazepine analogue with minimal intrinsic activity. It binds to the extracellular surface of GABAA receptors and competitively displaces benzodiazepine molecules, preventing further benzodiazepine binding. [10] Flumazenil can reverse respiratory depression in the rare patient with severe, isolated benzodiazepine or z-drug toxicity who does not have contraindications to its use. It is most often considered in accidental pediatric ingestions or reversal of iatrogenic oversedation. [11]
Contraindications to flumazenil use include the following [11] :
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Increased intracranial pressure (ICP) or closed head injury (CHI)
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History of epilepsy
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Unknown or mixed overdose,
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Benzodiazepine tolerance
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Prolonged QRS interval
In a meta-analysis, serious adverse events were significantly more common among patients with suspected benzodiazepine overdose treated with flumazenil than among those in the placebo group (12/498 versus 2/492; risk ratio: 3.81; 95% CI: 1.28–11.39; P = 0.02). The most common adverse events in the flumazenil group were agitation and gastrointestinal symptoms, and the most common severe adverse events were supraventricular arrhythmia and convulsions. [9] Seizures may become more difficult to manage and may require the use of propofol or barbiturates. A poison control center should be consulted if the use of flumazenil is being considered. [11]
If used, flumazenil should be administered slowly (0.2 mg/min up to 3-5 mg) because large doses cause agitation and withdrawal. The half-life of flumazenil is about 50 minutes and sedation often recurs. Cardiorespiratory monitoring is necessary, and repeat dosing or infusion may be required. [11]
Agent-specific interventions
Meprobamate: Force diuresis and provide hemodialysis in severe intoxication. Whole bowel irrigation is recommended for serious meprobamate poisoning because of the high predilection for bezoar formation.
Methaqualone (Quaalude): Do not provide diuresis. Diazepam can be administered for severe tonicity or seizures. Phenytoin may be strongly considered as an anticonvulsant because barbiturates potentiate this drug.
Chloral hydrate: Consider hemodialysis. Strictly avoid beta-adrenergic agonists (eg, dopamine) because they increase risk of fatal dysrhythmias. Beta-blockers (eg, propranolol) and overdrive pacing have also been reported to be effective. Intravenous propranolol is, perhaps, the drug of choice for chloral hydrate-associated ventricular dysrhythmias. Chloral hydrate sensitizes the myocardium to catecholamines, and propranolol blocks this effect. Lidocaine may also be used to treat ventricular dysrhythmias.
