Comment; It’s useful to have an idea of who won’t respond well to BZO’s so that other anti-seizure medications can be used to augment BZO treatment.

Editorial Comments by W Haning MD

Article authors; Neal J. BenedictCorrespondence information about the author Neal J. BenedictEmail the author Neal J. Benedict

Adrian Wong Elizabeth Cassidy Brian R. Lohr Anthony F. Pizon Pamela L. Smithburger Bonnie A. Falcione Levent Kirisci Sandra L. Kane-Gill


There is not much that is controversial about the management of withdrawal from long-term use of ethanol. As with other classes of drugs, generally, it is a matter of replacing like with like. But a particular focus of addiction medicine training, and a source of anxiety to all who staff consultation-liaison services, psychiatric or medical, is the management of alcohol withdrawal that appears poorly-responsive or even unresponsive to benzodiazepine (BZ) use. The authors of this embedded abstract have assigned an acronym, RAW, Resistant Alcohol Withdrawal; it might equally have been called “Runaway Alcohol Withdrawal,” for those familiar with the clinical presentation.  Once falling behind on the administration of a sedative-hypnotic, it is the very devil to catch up. The task is made more difficult by complications associated with the BZ preparations. Ethylene glycol derivatives, such as that used as a diluent for I.V. lorazepam, can actually reach toxic levels. The occasional failure to suppress withdrawal symptoms may reflect the narrow spectrum of receptor activity of BZs, when compared to ethanol; or it may have its source in another mechanism. But no one disputes the desirability of better predictive factors, that will allow anticipatory medication. The authors identify 5 in particular:

  • Thrombocytopenia doubles likelihood of benzodiazepine-resistant alcohol withdrawal.
  • (A) patient with psychiatric history (is) 2 times more likely to be benzodiazepine resistant.
  • (A) 1-unit increase (in) comorbidity or severity illness decreases benzodiazepine resistance [counter-intuitive – WFH].
  • Benzodiazepine-resistance (is) associated with abnormal admission liver enzymes.
  • Caucasian race and male gender (are)more predictive of benzodiazepine resistance.

Benedict NJ, et al., Predictors of resistant alcohol withdrawal (RAW): A retrospective case-control study.

Drug Alcohol Depend. 2018 Oct 2;192:303-308. doi: 10.1016/j.drugalcdep.2018.08.017. [Epub ahead of print]

736 patients (515 nRAW, 221 RAW) were analyzed. RAW patients were younger (P < 0.001), male (P = 0.008) Caucasians (P = 0.037) with histories of psychiatric illness (P < 0.001), higher serum ethanol concentrations (P < 0.007), and abnormal liver enzymes (P = 0.01). RAW patients had significantly lower platelets (P < 0.001), chloride (P = 0.02), and potassium (P = 0.01) levels; severity of illness (SAPSII) (P < 0.001) and comorbidity scores (P < 0.001). Caucasian race and male gender were found to be 3.6 and 2.6 times more likely to be RAW. For every 1-unit increase in comorbidity and severity of illness scores, patients were 22% [OR(95% CI) 0.78 (0.66–0.90)] and 4% [0.96 (0.93–0.98)] less likely to be RAW. Patients with a psychiatric history or thrombocytopenia were 2 times more likely [2.02 (1.24–3.30); 2.13 (1.31–3.50), respectively] to be RAW.

Dr. Raymond Oenbrink
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