Which medications in the drug class Benzodiazepines are used in the treatment of Delirium Tremens (DTs)?

Updated: Nov 06, 2020
  • Author: Michael James Burns, MD, FACEP, FACP, FIDSA; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Answer

Benzodiazepines

By acting on the GABA receptor, benzodiazepines produce a cross-tolerance to alcohol, thus reducing the hemodynamic and peripheral symptoms of alcohol withdrawal. The dose of benzodiazepine used should be based on the patient's symptoms and signs of alcohol withdrawal, including vital signs and amount of agitation. The longer-acting agents appear to be superior to the short-acting agents and may result in a smoother withdrawal course, with less breakthrough and rebound symptoms, although a risk of excessive sedation exists in certain patient groups (elderly patients, patients with liver failure) with the longer-acting agents.

For the treatment of minor or moderate alcohol withdrawal (in patients able to take oral therapy), symptom-triggered therapy (also known as prn therapy) has been shown in prospective, randomized, controlled trials to be superior to fixed-dose drug therapy, with less medication use and a shorter duration of therapy. The dosage of benzodiazepine needs to be individualized for each patient. The successful use of symptom-triggered therapy requires motivated and attentive nursing.

Drug regimens and doses recommended for minor withdrawal are not appropriate for patients with delirium tremens (DTs), who often require very high doses of these agents. For the treatment of DTs, benzodiazepines should be administered only parenterally.

For patients with severe withdrawal symptoms, including DTs, the benzodiazepine dose should be front loaded. That is, large doses should be administered intravenously at short intervals until the patient is calm but easily aroused. Then additional doses are administered only as needed. Most authorities recommend intravenous diazepam as the first choice for front-loading treatment of severe alcohol withdrawal. Because of its long serum half-life, and the even longer half-life of its active metabolite (desmethyldiazepam), additional doses may not be required once the patient is calm.

Longer-acting benzodiazepines (especially those with active metabolites) provide less fluctuation in blood levels and allow a more gradual physiologic taper. A review of 4 randomized controlled trials of front-loaded diazepam concluded that it produces a rapid calming effect with few untoward adverse effects in medically ill patients, required much less total dose of benzodiazepines, and resulted in a shorter duration of treatment, but may result in over sedation and respiratory depression in very elderly persons or those with severe liver disease. Aggressive treatment of severe alcohol withdrawal syndrome with diazepam may decrease the need for intubation.

Intravenous lorazepam, which has an intermediate serum half-life and no active metabolites, has been successfully used and may be preferable in elderly persons or in those with severe liver disease. Reports describe a higher incidence of late-onset alcohol withdrawal seizures with use of shorter-acting benzodiazepines such as oxazepam or lorazepam.

No controlled studies show superiority of shorter-acting agents (propofol, pentobarbital, lorazepam, and midazolam) over diazepam or other long-acting benzodiazepines.

If the IV route is not available, then intramuscular lorazepam (or midazolam as an alternative) is recommended. Diazepam and chlordiazepoxide should not be administered intramuscularly, because absorption is erratic.

The use of continuous IV infusions of short-acting benzodiazepines (lorazepam, midazolam) has been reported, but these infusions have required very large amounts of drug and are very expensive. No evidence indicates that continuous infusion therapy with short-acting agents leads to better outcomes than does oral or intravenous intermittent bolus therapy with long-acting agents.

Patients with DTs who do not respond to high doses of benzodiazepines may respond to the addition of phenobarbital, propofol, or possibly dexmedetomidine to the treatment regimen.

Chlordiazepoxide

Chlordiazepoxide depresses all levels of the central nervous system, including the limbic and reticular formations, possibly by increasing the activity of GABA, a major inhibitory neurotransmitter. The parenteral form is usually used initially. Because of limited experience with IV chlordiazepoxide for severe alcohol withdrawal and DTs, the use of IV diazepam or lorazepam is preferred.

Diazepam (Valium, Diastat)

Diazepam depresses all levels of central nervous system (eg, the limbic and reticular formations), possibly by increasing the activity of GABA. Individualize the dosage and increase cautiously to avoid adverse effects.

Because of its rapid onset, prolonged duration of effects, and high therapeutic index, diazepam is the drug of choice. Volumes of literature exist regarding the use of diazepam for ethanol withdrawal. The onset of action is within 5 minutes after IV administration. It has an active metabolite (desmethyldiazepam) that has a longer duration of action than that of diazepam.

Lorazepam (Ativan)

Lorazepam is a sedative hypnotic with a rapid onset of action and a medium duration of effect. By increasing the action of GABA, which is major inhibitory neurotransmitter in brain, it may depress all levels of the central nervous system, including the limbic and reticular formations. When the patient must be sedated for more than 24 hours, this medication is excellent, although it may require frequent redosing. Although diazepam is the preferred benzodiazepine, lorazepam is an excellent alternative and is especially useful in elderly persons and in those with severe hepatic dysfunction. It is commonly used prophylactically to prevent DTs. It can be given intramuscularly in patients lacking intravenous access.


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