Benzodiazepine overdose management

Weinbroum AA, Haishon R, Sorkine P. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Saf 1997 17 181-196. 

Flumazenil is an antidote that antagonizes actions of benzodiazepines on the CNS by blocking receptors. It is used for complete or partial reversal of sedative effects of benzodiazepines where general anesthesia is induced or maintained with benzodiazepines, where sedation is produced with benzodiazepines for diagnostic or therapeutic procedures, and for the management of benzodiazepine overdose. 

The primary indications for the use of flumazenil are the management of suspected benzodiazepine overdose and... 

B. Specific drugs and antidotes. Flumazenil (see p 446) is a specific benzodiazepine receptor antagonist that can rapidly reverse coma. However, because benzodiazepine overdose by itself is rarely fatal, the role of flumazenil in routine management has yet to be established. It Is administered intravenously with a starting dose of 0.1-0.2 mg, repeated as needed up to a maximum of 3 mg. It has some important potential drawbacks ... 

Seizures The use of flumazenil has been associated with the occurrence of seizures. These are most frequent in patients who have been on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic antidepressant overdose. Individualize the dosage of flumazenil and be prepared to manage seizures. 

Besides the paranoid psychosis associated with chronic use of amphetamines, a specific lesion associated with chronic amphetamine use is necrotizing arteritis, which may involve many small and medium-sized arteries and lead to fatal brain hemorrhage or renal failure. Overdoses of amphetamines are rarely fatal they can usually be managed by sedating the patient with benzodiazepines. 

Frequently, diazepam overdoses are adequately managed with clinical observation and supportive care. However, coingestion of ethanol and other CNS depressants which may exacerbate toxicity are common and warrant investigation in the patient history. Flumazenil, a benzodiazepine antagonist, effectively reverses symptoms of CNS toxicity, but is hazardous with the coingestion of other substances such as antidepressants. Therefore, it should not be used routinely. 

The basis of clinical management is supportive care. The airway should be secured and protected as needed. Symptomatic patients should have intravenous access and cardiac monitoring. Accidental ingestions exceeding 500-800 mg, and all intentional overdoses, should be treated with oral activated charcoal if patients present within 60 min of exposure. Seizures should be treated with benzodiazepines, or phenobarbital if refractory. Hypotension should be treated with intravenous fluids and vasopressors (dopamine or norepinephrine) if needed. Hemodialysis or hemoper-fusion may enhance elimination of both the parent compound and metabolites, but the clinical value of... 

Following a very large overdose of a benzodiazepine, a patient is admitted to hospital. Which one of the following is not likely to be of therapeutic value in the management of this patient ... 

Chlordiazepoxide Diazepam Midazolam Phenobarbital 54. Benzodiazepines are LEAST effective in (A) Alcohol withdrawal syndromes Balanced anesthesia regimens Initial management of phencyclidine overdose Obsessive-compulsive disorders Social phobias... 

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