#2 Get in the Spirit of Ambulatory Alcohol Withdrawal

Master the management of ambulatory alcohol withdrawal! We discuss the pathophysiology of alcohol withdrawal as well as the triage and treatment of this disease in the ambulatory setting. We’re joined by our bird-loving guest Dr. Stephen Holt (Yale University), an addiction medicine and internal medicine doc who teaches us a set of practical pearls that you won’t want to miss out on!

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Credits

Writer, Show notes, Infographics, and Cover Art: Shawn Cohen, MD
Hosts: Shawn Cohen, MD, Carolyn Chan, MD, Paul Williams MD
Reviewer: Era Kryzhanovskaya, MD
Showrunner: Carolyn Chan, MD
Technical Production: Castos
Guest: Dr. Stephen Holt, MD, MS, FACP

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Show Segments

Intro, disclaimer, guest bio
Guest one-liner, Picks of the Week*
Case from Kashlak
Who is at risk for alcohol withdrawal
Pathophys of alcohol withdrawal
Alcohol withdrawal timeline
Possible treatment locations
Triaging appropriate patients for this management
How to manage in the ambulatory setting (medication regimens, follow-up)
Why choose ambulatory alcohol withdrawal
Outro

Ambulatory Alcohol Withdrawal Pearls

Pathophysiology: Alcohol cools down the body (chronic GABA agonism). Alcohol withdrawal is like the body overheating after getting used to being cool for so long
Ambulatory management of alcohol withdrawal is safe, effective, and patient-centered for most people. Absolute contraindications to ambulatory management exist and include current or prior symptoms of severe withdrawal (e.g. seizures and delirium tremens).
For people with multiple comorbidities (liver disease, heart disease, renal disease), a discussion about the risks and benefits of ambulatory vs hospital-based management is appropriate. Patient-centeredness is the most important aspect of these discussions.
Benzodiazepines (diazepam and chlordiazepoxide) and gabapentin are effective regimens for ambulatory management and generally follow a 4-day taper schedule with several additional PRN doses
Follow-up with patients during the withdrawal period should ideally be every 1-2 days and telemedicine can be utilized. This can be done in any clinic!!!

Ambulatory Alcohol Withdrawal – Notes

Editor’s Note on language: The language we use is incredibly important and impactful, particularly around substance use. (Kelly 2010)

The term “detox” is used in this episode both to describe the physical location where people can be treated for alcohol withdrawal and the process of withdrawal. Since detox implies drug use–or someone currently using drugs–is toxic, the term is stigmatizing. We would advocate for the use of medically managed withdrawal or withdrawal management instead.

The term “relapse” is also used in this episode and is often found stigmatizing due to its association with the inaccurate moral model of addiction. We would advocate for the use of recurrence of use or return to use instead.

Who is at risk for alcohol withdrawal?

There are a number of factors that can increase an individual’s risk for the development of alcohol withdrawal. In Dr. Holt’s expert opinion, an individual who consumes 4-6 standard drinks every day for at least one month is likely to experience symptoms of alcohol withdrawal upon cessation or reduction of alcohol use.

Other risk factors for withdrawal include

Duration of alcohol use
Quantity of alcohol use
Prior history of alcohol withdrawal symptoms

Pathophysiology of Alcohol Withdrawal

You can think of neurotransmitters in the brain as a car. GABA is the primary inhibitory neurotransmitter which is analogous to a car brake, while glutamate can be thought of as the primary activating neurotransmitter – the gas pedal of the car. (Littleton, 1998)

Alcohol = GABA agonist

Chronic external GABA activation from alcohol leads to decreasing your internal GABA system (long-term alcohol use dismantles the brakes)
When the alcohol is taken away (withdrawal), disequilibrium occurs – glutamate goes into overdrive while GABA is nowhere to be found. This is where seizures can occur–the car is now speeding without brakes!

Alcohol Withdrawal Syndrome (AWS)

Even reductions in alcohol (e.g. cutting back from 2 pints daily to 1 pint daily), not just cessation, can lead to withdrawal symptoms. With each subsequent course of alcohol withdrawal, the withdrawal symptoms are more likely to become severe or present in a worse fashion. This is referred to as the alcohol kindling phenomenon (Becker, 1998).

AWS – Symptoms and Timeline

One can think about alcohol withdrawal in 3 ways: early or mild alcohol withdrawal symptoms, alcohol-induced hallucinosis, and severe/complicated alcohol withdrawal.

Early or mild withdrawal symptoms are primarily in the first ~24hrs after last drink (or dramatic reduction in drinking) and are the subjective findings and symptoms that make up the CIWA-Ar (Clinical Institute for Withdrawal for Alcohol, revised) score that is often used for hospital withdrawal management. Symptoms include nausea, GI upset, tremors, anxiety, headaches, and skin-crawling sensation.

Alcohol hallucinosis can start on days 2 – 3 in a small subset of individuals (Stephane, 2018).

Hallucinations can be tactile, auditory, visual
People have a normal orientation throughout and the hallucinations are generally ego-dystonic–a person remains oriented but feeling, hearing, seeing things that aren’t there and the hallucinations are bothering them.
No sympathetic stimulation (not tachycardic or hypertensive)

Severe or complicated alcohol withdrawal generally starts on days 3-4. This is the SCARY withdrawal and can lead to death.

Symptoms can include:

Seizures
Sympathetic overdrive – tachycardia, hypertension, hyperthermia
Acute agitated delirium – disorientation which may be accompanied by agitation, hallucinations
Delirium Tremens (DTs) generally refers to the combination of delirium and sympathetic overdrive

Expert opinion (Dr. Holt)– Take into account the last 3 months of their alcohol withdrawal history when thinking about the impact of kindling (especially on the brain) and the risk of severe withdrawal.

Expert opinion (Dr. Cohen) – My favorite diagram of alcohol withdrawal symptoms/timeline is from this publication (Kattimani, 2013)

Of note, in one study of 1024 individuals referred for ambulatory management of alcohol withdrawal without any pharmacotherapy, only 1% of individuals experienced seizures (Whitifeld, 1978).

Treatment Locations for AWS

While most training emphasizes hospital treatment of alcohol withdrawal, the vast majority of individuals who experience alcohol withdrawal can be managed in the outpatient setting. In the middle of the spectrum of treatment settings are medically managed withdrawal centers (“detox centers”).

The most recent ASAM Alcohol Withdrawal Guideline outlines the different treatment settings and when to choose them but is quite detailed and complex (ASAM).

Expert opinion (Dr. Cohen): The simplest way to determine location is to evaluate someone for the safety of ambulatory withdrawal management. What are the absolute/relative contraindications for outpatient treatment and are they present for the patient in front of us? If it’s not safe, then they should be evaluated in an emergency room. Hospitals often have relationships with local substance use disorder (SUD) treatment facilities for medically managed alcohol withdrawal and can refer to other levels of treatment if hospitalization is not needed.

Why consider ambulatory alcohol withdrawal management?

The most robust data supporting ambulatory alcohol withdrawal is a randomized controlled trial comparing ambulatory and hospital management of alcohol withdrawal and found no difference in complication rates but a shorter length of treatment and lower costs with ambulatory management (Hayashida 1989).

One of the biggest benefits is avoiding the hospital and building trust with your patient. Avoiding the hospital when able is a huge win for both clinicians and patients. Showing you’re able to help someone do that and managing what is an often stigmatized condition can help build trust with your patient as well.

Who is appropriate for ambulatory alcohol withdrawal management?

First, triage patients who are at risk for severe withdrawal and patients in whom any significant withdrawal can lead to medical complications. Those individuals should be referred to the inpatient setting for AWS management

As we discussed above, if most patients can be managed in the outpatient setting (the standard), we can think about absolute and relative contraindications to this standard of alcohol withdrawal management.

Absolute Contraindications to Ambulatory AWS Management:

Prior history of severe/complicated AWS (DTs, seizures) (Wood et al, 2018)
Currently in moderate or severe/complicated withdrawal in the clinic office

Relative Contraindications to Ambulatory AWS Management:

Risk vs benefit discussions should occur with the patients who have the following characteristics to determine where the optimal location is for an individual to have their AWS managed:

Comorbidities – 4Cs (CHF/heart failure NYHA Class 2+, decompensated cirrhosis, CKD Stage 3+, COPD on O2) and unstable psychiatric disease
Pregnancy
Psychosocial complexity – homeless, living alone, transportation barriers, or no access to telehealth
Multiple other active substance use disorders
Other significant sedating medications

Harm Reduction Tip: Some patients may decline to go to the hospital for AWS management, and for those certain individuals, it may be safer to trial a supervised ambulatory AWS than receive no medical care at all for their AWS. Dr. Holt documents the conversation around this and how providers can meet the patient where they are at with treatment settings.

Management of AWS

Clinic Support

There are no specific clinic requirements to do this other than the capacity to follow up ideally every day or every other day. This could be via telehealth or an in-person visit.

Medications

The two primary treatment options are benzodiazepines (preferentially long-acting benzodiazepine like diazepam–for a “gentler withdrawal course”) and gabapentin. Both courses are generally a 4-day taper, in addition to PRN doses. It’s often best to set the expectations that the first day of treatment is not the day of the visit and start on a fresh day in the morning.

Expert opinion (Dr. Holt): If someone drinks more than 10 standard drinks in a day, opt for a higher medication dose on day 1. Increase diazepam to 20mg Q6H, chlordiazepoxide 100mg, or gabapentin to 600mg Q6H on day 1. If an individual drinks LESS than 10 standard drinks a day, opt for diazepam 10mg Q6H, chlordiazepoxide 50mg, or gabapentin 300mg Q6H on day 1. Days 2-4 approaches are the same regardless of # of drinks. Prescription allows for one PRN dose per day.

Consider benzodiazepines as the first line and choose gabapentin instead in someone for whom you expect the withdrawal course to be milder. A bonus for gabapentin is that it can be continued as an effective long-term medication for AUD (Mason 2014). Gabapentin may also reduce the alcohol kindling phenomenon (Stock, 2013).

Other Options: Can also consider carbamazepine as a reasonable alternative option. Although this is less commonly used in the United States, it is a co-first-line medication in the NICE (UK) guidelines. The use of other medications (phenobarbital, valproic acid, baclofen, clonidine) for ambulatory alcohol withdrawal doesn’t have significant supportive data so would avoid them in ambulatory management at this time.

Follow Up

In an ideal scenario, the clinic and patient should have the ability to check in daily on the phone or every other day using some visual means. This can be accomplished with office visits but doesn’t need to be, telephone and video visits work well and can be much more accessible.

During these visits, you’re getting a sense of their symptoms (think again about what’s asked in a CIWA score- nausea, GI upset, tremors, anxiety, headaches, skin-crawling). You’re also getting a sense for markers of withdrawal becoming more severe (disorientation or seizures which would prompt hospital evaluation) or oversedation from medications.

You can consider the use of a more formalized scale for symptoms like the Short Alcohol Withdrawal Scale/SAWS (Muncie, 2013) to gauge if things are getting worse or better.. It can also be helpful to get collateral from someone supporting a patient through the withdrawal course when able.

Expert opinion (Dr. Holt) – You don’t need to use a formalized symptom score to guide the assessment here. Use your clinical gestalt.

Supportive Care

While labs are not necessary for this process, if a patient can get labs consider getting a CMP to assess liver and renal function (plus this can serve as an opportunity to get indicated screening labs too – viral hepatitis, HIV).

The topic of vitamin deficiencies is an important one to discuss as well. Thiamine deficiency in people who use alcohol is underdiagnosed (Caine 1997) and its impacts (Wernicke’s encephalopathy) can be reversed if treated early.

But treatment with oral thiamine is poorly absorbed and true treatment of Wernicke’s encephalopathy requires a high dose of IV thiamine multiple times daily (Latt 2014). Prescribing a multivitamin and thiamine is easy, but given unclear benefits and additional pill burden, it is worth prioritizing more evidence-based interventions like medications for alcohol use disorder (MAUD) instead (DeFries 2021).

Alcohol use disorder is a chronic disease and like many chronic diseases, the clinical course often involves recurrences. A return to alcohol use does not represent a failure of ambulatory withdrawal management or a failure by the patient (see our note on language). Engagement in ambulatory management of alcohol withdrawal is an opportunity to engage a person in the treatment of their alcohol use disorder with medications (see the future episode on MAUD) and addressing the other drivers of their alcohol use (e.g. housing status, prior or current trauma, mental health, employment).

For a great guide on reducing the harm of alcohol use check this out. (Harm Reduction Research and Treatment Center)

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