In this episode I’ll discuss how to use dexmedetomidine in severe alcohol withdrawal.
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Dexmedetomidine
Dexmedetomidine is an Alpha2-Adrenergic Agonist sedative agent.
As discussed in episode 70 on severe alcohol withdrawal, dexmedetomidine reduces sympathetic outflow and blunts many of the symptoms of alcohol withdrawal, including:
Tremor
Tachycardia
Anxiety
Agitation
Effects on symptom-triggered benzodiazepine use
Many of the symptoms of withdrawal that dexmedetomidine affects are part of the CIWA-AR or CIWA-AD withdrawal scoring protocols.
This effectively means that when dexmedetomidine is started, patients will score lower on withdrawal scoring protocols and therefore receive benzodiazepines less often.
The side effects of benzodiazepines can be significant – namely delirium and respiratory failure.
However GABA sensitivity is significantly altered in patients with alcohol withdrawal, and all other treatments considered effective (benzodiazepines, phenobarbital, propofol, gabapentin) have some activity on GABA receptors.
Dexmedetomidine lacks any GABA activity. It does not prevent seizure associated with severe alcohol withdrawal. Due to the lower benzodiazepine dose patients on dexmedetomidine receive, they also receive less stimulation of GABA receptors.
Evidence
Has the significance of this effect been studied?
Brian Hayes (@PharmERToxGuy on Twitter) has previously examined the quality of the evidence for dexmedetomidine for alcohol withdrawal. He points out that the endpoints in available clinical trials are the wrong ones to look at:
@PharmacyJoe There is a limited role for dexmedetomidine in EtOH withdrawal; available data looks at wrong endpoints https://t.co/09H4t8c6UF
— Bryan D. Hayes (@PharmERToxGuy) September 4, 2016
So what exactly does the available literature on this subject cover?
2015: Dexmedetomidine reduced benzodiazepine requirements during ICU stay.
One study that did have clinically relevant endpoints was terminated due to slow enrollment. No results for that study are posted.
Considering that dexmedetomidine has been available for over a decade, I would expect we would know more about its effects when used as an adjunct in alcohol withdrawal.
A 1987 study that examined clonidine in alcohol withdrawal concluded: The alpha-2-adrenergic agonists in alcohol treatment seemed modestly effective for treatment of some parts of alcohol withdrawal. They represent a promising, novel, but still investigational approach. Additional data, particularly comparing them to the benzodiazepines, are needed before their potential in therapeutics can be assessed.
Nearly 30 years later it seems we are in the same position as to the level of evidence available to make a judgment on how to use dexmedetomidine for alcohol withdrawal.
Conclusion
I remain concerned that when dexmedetomidine is added to a patient in alcohol withdrawal, symptom-triggered dosing of benzodiazepines comes to a halt. To attempt to counter this, I ask for a scheduled benzodiazepine regimen to be added.
Another option that makes sense would be to cap the dexmedetomidine dose at a low level (0.5 mcg/kg/hr) in hopes that the patient would still score enough on a CIWA scale to still receive enough benzodiazepines to treat their withdrawal. If this is done I would use frequent doses of diazepam (10 mg every 10 minutes prn withdrawal) to ensure the safety of the staff involved in caring for the patient.
Given the scant evidence beyond short-term improvements in sedation or benzodiazepine dose, I expect there is a lot of variability in how dexmedetomidine is used in severe alcohol withdrawal. Leave a comment below to let me know how you use dexmedetomidine to treat alcohol withdrawal.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Joe, thanks for taking on this topic and for highlighting our review at ALiEM.com. Your suggestion of possibly capping the dexmedetomidine dose so as not to fully mask the withdrawal symptoms (and prevent adequate benzodiazepine administration) is an interesting one. Hopefully, there will be some better studies published at some point. For the listeners, Dr. Lewis Nelson and I published a letter-to-the-editor on the most recent trial in Journal of Intensive Care Medicine. Here is a link to our LTE, which further emphasizes the weaknesses in available data: https://www.dropbox.com/s/r1qv3stobk2w39e/J%20Intensive%20Care%20Med-2016-Hayes-353-4.pdf?dl=0
Thank you Bryan for the comment and link to your letter-to-the-editor! I like your explanation & critical appraisal of that study & the endpoints.
Also, congratulations on starting pharmertoxguy.com!!! I’ve signed up to follow your blog & will be watching that space for more from you!
The few studies looking at precedex in severe ETOH withdrawal have either been negative or inconclusive or as you mentioned, looking at arguably pointless outcomes. This drug is expensive and requires titration. IMHO, has no role in this setting. Better to use escalating doses of the one and only class of drugs we know work (benzos) alongside supportive care. Enjoyed your post.
Just brought a patient to the ICU in DTs. Ativan 2mg q15 min wasn’t effective. I’m a gastroenterologist and use IV sedation for procedures, so I’m comfortable with the occasional high dose of benzodiazepines. I pushed a total of 60 mg of diazepam over 5 minutes or so and still not much effect (still trying to get out of bed, but wasn’t putting his legs over the edge as much). Precedex no running aat 0.8. The hospital here sees a lot of DTs and nursing knows about the need for benzodiazepams to prevent seizures. I agree with “IM guy says” mostly, but when the benzodiazepam dose becomes high enough it is helpful to have a mixed technique.