In this episode I’ll discuss the treatment of severe alcohol withdrawal.
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Symptoms
Symptoms of alcohol withdrawal are the result of an increase in autonomic activity and sympathetic outflow, as well as psychomotor agitation. Commonly this manifests as diaphoresis, nausea, vomiting, tremor, and anxiety.
Severe alcohol withdrawal may progress to seizures and/or delirium tremens.
Treatment
The goal of treatment is to reduce the severity of symptoms and prevent progression to delirium tremens.
It is widely accepted that the best way to treat alcohol withdrawal in hospitalized patients is with symptom triggered benzodiazepine therapy. Such treatment results in equivalent outcomes and less benzodiazepine use compared with scheduled benzodiazepine therapy.
The use of symptom-triggered therapy has yet to be studied prospectively in patients requiring intensive care for severe alcohol withdrawal.
Evidence for treating severe alcohol withdrawal is limited to retrospective pre/post intervention reviews. From the available evidence, it appears that escalating doses of diazepam up to 100 mg per dose or more is a reasonable approach.
Diazepam
Diazepam is an ideal benzodiazepine to use for severe alcohol withdrawal. It is available in IV and oral form and has active metabolites which might provide longer duration of action and smoother clinical course.
The need for mechanical ventilation was reduced in two studies when protocol-based escalating doses of diazepam were used. One of the studies found a trend in decreased ICU length of stay while the other found a significant decrease from 9.6 to 5.2 days using protocol-based escalating doses of diazepam.
The protocol-based escalating doses of diazepam for severe alcohol withdrawal were dosed to a target RASS goal of 0 to -2. The diazepam dose increased every 10 minutes up to 100-150 mg per dose. If agitation was not controlled at these doses, phenobarbital was added. If this did not work, continuous sedation and mechanical ventilation were employed.
It is counter-intuitive that high doses of benzodiazepines might prevent mechanical ventilation, but that is what the evidence suggests.
Dexmedetomidine
Noticeably absent from these studies is the use of dexmedetomidine. As an alpha-2 agonist, dexmedetomidine reduces sympathetic outflow and blunts many of the symptoms of alcohol withdrawal. Dexmedetomidine is not appropriate for monotherapy in severe alcohol withdrawal as it lacks the GABA receptor activity required to prevent seizures.
Many clinicians perceive that dexmedetomidine has the potential to spare the need for intubation in severe alcohol withdrawal. So far evidence only demonstrates that dexmedetomidine has the potential to reduce the use of benzodiazepines. Whether this translates to a decrease in length of stay or mortality is yet to be seen.
In my own practice I find that dexmedetomidine is added too soon to patients with severe alcohol withdrawal. Often this is done before significant doses of benzodiazepines have been used.
Adding dexmedetomidine complicates the assessment of the symptoms of alcohol withdrawal. If only “as needed” doses of benzodiazepines are ordered, dexmedetomidine often ends up being used as monotherapy. This leaves the patient at risk of alcohol withdrawal seizures. Anecdotally, I find these patients also have prolonged alcohol withdrawal symptoms.
If dexmedetomidine is used for a patient with severe alcohol withdrawal, I insist on a regimen of scheduled benzodiazepine doses.
Thiamine
Thiamine supplementation is an important part of the treatment of alcohol withdrawal. Thiamine levels are often deficient in patients with alcohol withdrawal. This can lead to the development of Wernicke’s Encephalopathy.
IV thiamine for the treatment and prophylaxis of Wernicke’s Encephalopathy has generally been considered inexpensive and without significant side effects. For these reasons organizations such as the Royal College of Physicians in the UK have recommended large IV thiamine doses such as 500 mg q8 hrs for treatment and 250 mg q24 hrs for prophylaxis of Wernicke’s Encephalopathy.
Review
A recent review of severe alcohol withdrawal was published in Annals of Pharmacotherapy.
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Curious about your anecdotal evidence for prolonged etoh withdrawal associated with precedex monotherapy (or mostly monotherapy).
In my practice I have noticed an increase in patients who end up intubated in the ICU on mostly precedex for their etoh withdrawal. The patients get some benzos, but surely not as many as they would get without the precedex on board. These patients tend to be encephalopathic for 1-3 weeks after their acute ETOH withdrawals have passed. Wondering if this matches what you are seeing?
Look forward to your reply!
Steph
Yes! That is exactly what I am seeing…I seem to remember a paper suggesting this happened more with dexmedetomidine but I can’t put my finger on the reference.
This has been my experience as well “I find that dexmedetomidine is added too soon to patients with severe alcohol withdrawal. Often this is done before significant doses of benzodiazepines have been used”…well said.
I think dexmedetomide is often started because we aren’t giving enough BZD to these GABA receptor starved patients…
Several of my friends trained at LA county where the following stepwise protocol is utilized (and sometimes initiated for severe etoh w/d in my ER):
Ativan 2mg IV push, then 4mg then 8mg then 16mg then 32mg IVP; if s/s/x not controlled then Phenobarb 130mg IVP, then Phenobarb 260mg IVP, then Propofol gtt. Pts usually get tubed between the 16 – 32mg Ativan mark but I like how this illustrates “Do not be afraid of aggressive BZD dose escalation in severe ETOH W/D”. BZD are dangerous in ETOH toxicity but not so much in ETOH w/d. Opposite to Haldol IE not good for ETOH W/D but Good in Combative ETOH Toxic pt.
Another excellent review Joe…Thank you!
Thank you!
Hi Joe
Great review. However, with the shortage of Diazepam IV, what doses of Lorazepam would you substitute for Diazepam?
Thanks
Thank you Mervyn!
I consider 1 mg of lorazepam to be approximately equivalent to 5 mg of diazepam.