Refractory delirium tremens

Q: How is "refractory delirium tremens" usually defined?

Answer: Refractory delirium tremens is also called "benzodiazepine-resistant alcohol withdrawal." Although no absolute definition exists for clinically unresponsive patients, IV administration of more than 50 mg of diazepam or 10 mg of lorazepam during the first hour of treatment or 200 mg of diazepam or 40 mg of lorazepam during the initial three to four hours of treatment is considered resistant.

The reason could be the low endogenous GABA concentrations or acquired conformational changes in the GABA receptor.

Such patients need more aggressive or next-level treatment with phenobarbital, propofol, and dexmedetomidine. Most of these patients usually require mechanical ventilation.

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References:

1.  Langlois H, Cormier M, Villeneuve E, et al. Benzodiazepine resistant alcohol withdrawal: What is the clinician's preferred definition? CJEM 2020; 22:165.

2. Lindsay DL, Freedman K, Jarvis M, et al. Executive Summary of the American Society of Addiction Medicine (ASAM) Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med 2020; 14:376.

3. Schmidt KJ, Doshi MR, Holzhausen JM, et al. Treatment of Severe Alcohol Withdrawal. Ann Pharmacother 2016; 50:389.

4. Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63:53.