Phenobarbital For Alcohol Withdrawal

At the beginning of my medical training, I grew accustomed to benzodiazepines like lorazepam, chlordiazepoxide, and diazepam being used as the cornerstone of therapy for alcohol withdrawal based on symptoms and the Clinical Institute Withdrawal Assessment of Alcohol (CIWA) protocol. During my ICU fellowship, I transitioned over to using phenobarbital – a barbiturate with sedative and anticonvulsant properties that depresses cortical activities to also achieve hypnosis. Furthermore, the literature (and pharmacology) suggest less paradoxical reactions with barbiturates compared to benzodiazepines. Furthermore, barbiturates stimulate GABA (inhibition) while driving down glutaminergic (excitatory) activity. Win-win! 🙂

In patients with severe alcohol withdrawal histories (ie, withdrawal seizures, delirium tremens, prior ICU admissions for detoxification, benzodiazepine resistance/paradoxical reactions), phenobarbital therapy may be especially advantageous! However, if patients have a history of prior Stevens Johnson syndrome or toxic epidermal necrolysis (SJS/TEN) or acute intermittent porphyria (AIP), I tend to be wary.

So how does this actually work?

First, I try to stratify the risk for respiratory depression based on concomitant benzodiazepines/opioids, pulmonary reserve, age, etc. Then I’ll load phenobarbital over 30 minutes based on ideal body weight: 12-15 mg/kg for low risk, 8-12 mg/kg for medium risk, and 5-8 mg/kg for high risk. If the patient has active symptoms of withdrawal or recent alcohol use, then I’ll usually opt for a higher loading dose.

If active signs of withdrawal persist after the loading infusion (tremor, sweating, delirium, etc.), I’ll consider intravenous administration anywhere from 130 – 260 mg every 30-60 minutes as needed.

Once patients have stabilized and moved to a step-down or general medical-surgical floor bed, they can get oral phenobarbital (100-200 mg every hour) depending on the severity of their symptoms.

An important caveat is that other respiratory depressants should be used with extreme caution! Furthermore, other etiologies of delirium must be considered over the course of hospitalization if patients seem to remain refractory to therapy (ie, stroke, electrolyte abnormalities, polypharmacy, pain, sepsis, etc.)

Drop me a comment below with questions! 🙂

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    1. Great point! Just like all things, I’d prioritize the more life-threatening issues first. Acute withdrawal (especially delirium tremens) has an independent morbidity/mortality associated with it. Gotta get that under control first!

  1. We do hundreds of alcohol detoxifications a year and our standard medication is oral clomethiazole (syrup for easy dose adjustments or capsules) combined with levetiracetam as anticonvulsant prophylaxis. Only in severe casis we add on a benzo (oral lorazepam or i.v. midazolam) and/or clonidine. This usually works wonders. Don’t forget the Vit B1.

  2. As an RN in a rough and tough small town ICU, I often get individuals in alcohol withdrawal, especially ones who have had seizures before…this has never been ordered and I have never heard of it before but will recommend going forward. Thank you for this caveat of knowledge!

  3. Completely agree! I always encourage my attendings to consider phenobarb over benzos. There is, now, plentiful literature available, and anecdotally, I’ve seen it work wonders at the bedside (not to mention it significantly reduces the nursing burden ?).

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