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?

2016: When dexmedetomidine was started within the first 60 hours of hospital admission, fewer benzodiazepines were used at 12 or 24 hours.

2016: Dexmedetomidine did not affect ICU or hospital length of stay compared with propofol when used as an adjunct in alcohol withdrawal.

2016: Dexmedetomidine use was associated with a doubling of the hospital and ICU length of stay (8.9 days vs 4.7 days; p < 0.01; and 2.9 days vs 1.4 days, p < 0.01, respectively).

2015: Dexmedetomidine reduced benzodiazepine requirements during ICU stay.

2015: Seizures have been reported with dexmedetomidine due to lack of γ-aminobutyric acid agonist administration.

2015: Dexmedetomidine reduces hypertension and tachycardia in AWS and also reduces benzodiazepine requirements; however, the impact of these findings on important clinical endpoints is yet to be determined.

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.

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