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- W2078163007 abstract "We read with interest the study by Khan et al.1 regarding predictors of mortality in patients with delirium tremens. We agree that the finding of restraint use as a predictor of mortality likely represents inadequate chemical sedation. In their discussion, the authors describe benzodiazepines as the most suitable approach to management of these patients, due to their strong agonist effect at the GABAA receptor. While this holds true for many patients with alcohol withdrawal symptoms, increased understanding of GABAA receptor–ethanol interactions should compel us to update our approach to the management of delirium tremens. It has been shown that chronic exposure of GABAA receptors to ethanol results in a change in the specific GABAA receptor subtypes that are expressed in the brain. Specifically, there is decreased expression of benzodiazepine-sensitive receptors containing alpha 1 and alpha 2 subunits and increased expression of receptors with alpha 4 and alpha 6 subunits, which are completely unresponsive to benzodiazepines.2 Consistent with this finding, a population of alcohol withdrawal patients who are resistant to treatment with benzodiazepines has been described.3 Continued attempts to achieve sedation using only benzodiazepines in patients who may possess a “resistant” population of GABAA receptors, and who have demonstrated limited or no clinical response to hundreds of milligrams of benzodiazepines, may prolong or worsen agitation (thus increasing the chance they will be physically restrained), hyperthermia, and rhabdomyolysis and possibly increase risk of death. In such cases, an alternative therapy is warranted. Barbiturates are potent GABAA agonists that bind the receptor at a site separate from the benzodiazepine binding site.4 In our practice, once patients have received several hundred milligrams of diazepam without good clinical response, we immediately switch to phenobarbital. We have had excellent experience using phenobarbital in benzodiazepine-resistant patients. In the most severe cases, where benzodiazepines as well as 20 mg/kg phenobarbital do not reverse symptoms of alcohol withdrawal, we have found the addition of propofol to be effective. Propofol activates the GABAA receptor and has also been shown to antagonize excitatory NMDA glutamate receptors in vitro.5, 6 With any of these therapies close attention to the airway is important, and intubation will likely be necessary with the use of propofol. With recognition of delirium tremens as a life-threatening condition that may not be effectively treated with even high doses of benzodiazepines, mortality resulting from delirium tremens in the hospital setting may disappear." @default.
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- W2078163007 date "2009-01-01" @default.
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- W2078163007 title "Letters on “Predictors of Mortality in Patients with Delerium Tremens”" @default.
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- W2078163007 doi "https://doi.org/10.1111/j.1553-2712.2008.00307.x" @default.
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