#16 Distilling Inpatient Alcohol Withdrawal with Dr. Shawn Cohen

August 3, 2023 | By Carolyn Chan

Audio

Video

Distill the management of inpatient alcohol withdrawal down to its core with Dr. Shawn Cohen (@ShawnCohen_MD, Yale University). This episode is full of practical pearls, and we discuss the ins and outs of managing alcohol withdrawal in the hospital setting.  Learn how to triage patients in the hospital, which benzodiazepines to select, the pathophysiology of alcohol withdrawal, and phenobarbital for the management of alcohol withdrawal. 

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Production Partner: ACAAM

The Curbsiders Addiction Medicine are proud to partner with  The American College of Addiction Medicine (ACAAM) to bring you this mini-series.  ACAAM is the proud home for academic addiction medicine faculty and trainees and is dedicated to training and supporting the next generation of academic addiction medicine leaders. Visit their website at acaam.org to learn more about their organization.

Show Segments

• Intro 0:00
• Guest bio – 3:17
• Case 1- 5:20
• Alcohol withdrawal pathophysiology – 6:10
• Kindling effect –  9:05
• Diagnosing alcohol withdrawal and clinical withdrawal scales – 10:12
• Severe alcohol withdrawal definition – 15:26 
• Triaging a patient – 16:50
• Medication management for alcohol withdrawal syndrome- 19:37
• Decisions between benzodiazepines and phenobarbital and formulation – 23:47
• Choices of benzodiazepines in hepatic impairment – 26:30 
• Symptom triggered vs. fixed protocol – 28:10
• Benzodiazepine resistant alcohol withdrawal – 33:33
• Timeline of alcohol withdrawal syndrome symptoms – 42:38
• ICU management of alcohol withdrawal – 46:27
• Discharge planning and management of alcohol use disorder – 48:50
• Take home points – 51:45
• Lightning round- 53:43
• Outro – 56:01

Distilling Inpatient Alcohol Withdrawal Pearls

1. Alcohol withdrawal is a clinical syndrome and diagnosis. It requires the right clinical context (e.g. the removal or decrease of chronic alcohol use) and symptoms (e.g.. tremors, agitation, seizure, delirium tremens) to make the diagnosis.
2. Alcohol withdrawal is the result of an imbalance of GABA (inhibitory) and glutamate (excitatory) signaling in the brain. An increase in glutamate can result in symptoms such as tremors, agitation, autonomic hyperactivity, hallucinosis, nausea/vomiting, seizure, and delirium tremens (DTs).
3. Clinical scales can help clinicians (i.e. CIWA-Ar, MINDS, RASS) triage and understand the severity of the syndrome.
4. Benzodiazepines are the mainstay of treatment of alcohol withdrawal – generally, long-acting and symptom-triggered benzodiazepine protocols are preferred, resulting in shorter hospital lengths of stay. 
5. Phenobarbital can be used instead of benzodiazepines and can be particularly helpful in treating severe alcohol withdrawal and benzodiazepine-resistant alcohol withdrawal.
6. Offer patients treatment for their alcohol use disorder in the hospital including medications such as naltrexone, acamprosate, and disulfiram. 

#16 Distilling Inpatient Alcohol Withdrawal Management 

Definitions

Alcohol Withdrawal Syndrome: 

Alcohol is a CNS depressant. Chronic alcohol use requires more of the inhibitory neurotransmitter GABA to be needed in the body to maintain inhibitory tone. Over time the body compensates by upregulating the excitatory neurotransmitter glutamate to compensate. When someone is using enough alcohol (around 4 drinks) consistently (over at least two weeks), their brain may make these changes.

Alcohol withdrawal occurs, if chronic alcohol use has been removed or decreased. This causes there to be an excess of the excitatory glutamate signals that have been up-regulated leading to the clinical signs of alcohol withdrawal we associate with tremors, agitation, nausea/vomiting, hallucinosis, seizure, and delirium tremens. 

Alcohol withdrawal syndrome is a clinical diagnosis – one based on the correct clinical scenario and symptoms we attribute to alcohol withdrawal. DSM 5 criteria include 

• Cessation or reduction in alcohol use that was previously heavy and prolonged
• Two or more of the following develop hours to days after cessation or reduction: Autonomic hyperactivity, increased hand tremor, insomnia, nausea/vomiting, transient visual or tactile or auditory hallucinations, psychomotor agitation, anxiety, and generalized tonic-clonic seizure 
• The symptoms above cause clinically significant distress or impairment in other important areas of function 
• Signs and symptoms are not attributable to another medical condition. 

Mild to moderate withdrawal symptoms may include tremors, agitation, diaphoresis, nausea, and tongue fasciculations. More severe symptoms include seizures and delirium tremens.

The timeline below is a general picture of when to expect specific symptoms of alcohol withdrawal, although these observed patterns and certain symptoms may appear at different time points than below (Kattimani, 2013).  

• 6-36 hours – Minor symptoms including nausea, agitation, tremors, autonomic hyperactivity
• 6-48 hours – seizures
• 12-48 hours – hallucinosis (e.g. visual, auditory, or tactile hallucinations with intact orientation)
• 48-96 hours – delirium tremens (e.g. agitation, hypertension, fever, diaphoresis, delirium)

Kindling Effect 

The kindling effect is the idea that the more often a person experiences alcohol withdrawal syndrome, the more severe their alcohol withdrawal symptoms are likely to be (Becker 1998). This is the basis for the idea that if someone has had severe alcohol withdrawal in the past, they are likely to experience this again and so may need more aggressive treatment.

Clinical scales

There are various clinical scales used, not to diagnose alcohol withdrawal, but instead to measure severity and guide therapy. Examples of these clinical withdrawal scales include: 

• CIWA-ar – Clinical Institute Withdrawal Assessment for Alcohol, Revised (Sullivan, 1989)
• MINDS – Minnesota Detoxification Scale (DeCarolis, 2007)
• RASS – Richmond Agitation Sedation Scale (Sessler, 2002)

The use of these clinical scales is institutionally dependent. Dr. Cohen recommends using the scale that one’s clinical staff are familiar with to direct treatment.

The severity of alcohol withdrawal is often defined and understood using these clinical withdrawal scales. CIWA-Ar scores of <10 constitute mild alcohol withdrawal, 10-18 moderate, and >18 severe (ASAM Clinical Practice Guideline on Alcohol Withdrawal Management).  Dr. Cohen notes that there is a lack of consensus on what CIWA cutoff represents severe withdrawal, as different cutoffs have been used in a variety of studies. 

Admission and triage of the patient experiencing alcohol withdrawal: 

Not all patients experiencing alcohol withdrawal need to be admitted. Considerations include a history of severe alcohol withdrawal, support system at home, mild severity of current symptoms, and comorbidities (as discussed in Curbsiders Addition Medicine Episode #2). 

Once the decision has been made to admit a patient, Dr. Cohen recommends utilizing a patient’s history to help guide the triage decision as to where the patient should be admitted. Consider the following: 

• Have they experienced severe alcohol withdrawal in the past?
• What is their presenting symptom? Seizures happen early in the course of alcohol withdrawal and these patients should be carefully triaged and may require higher levels of care and more aggressive therapy. 
• What are their current symptoms as compared to their blood alcohol level? If they are already experiencing many symptoms and the blood alcohol content is still high, they will likely continue to get worse. 
• What other co-morbidities and current issues is someone experiencing? The goal is to understand whether they will be able to medically tolerate alcohol withdrawal or not. 

Treatment of Alcohol Withdrawal in the Inpatient Setting

Thinking about the underlying pathophysiology of alcohol withdrawal (too little GABA in comparison to glutamate signaling), the mainstay of therapy is giving GABA-ergic medications. The therapy with the most evidence base is benzodiazepines which act on GABA receptors (Amato, 2010). 

Selection of Benzodiazepines:

Dr. Cohen recommends long-acting benzodiazepines over short-acting ones,  as this may help prevent breakthrough symptoms of withdrawal. There is mixed evidence in the research of one benzodiazepine over the other, with some studies pointing to long-acting (diazepam, chlordiazepoxide etc.) options being more effective at preventing seizures than shorter-acting options  (Mayo-Smith, 1997). In Dr. Cohen’s expert opinion, he often uses diazepam, given it is available in PO, IV, and IM formulations and has a rapid time to onset, making it ideal for acute withdrawal settings. As with clinical withdrawal scales, the types of benzodiazepines available vary from institution to institution – he recommends using the protocol in place at your institution for consistency. 

A common question is what benzodiazepines to choose in patients with liver dysfunction. Benzodiazepines that are safer to use in patients with liver dysfunction can be remembered with the pneumonic “L.O.T” – lorazepam,  oxazepam, and temazepam. All three of these benzodiazepines undergo hepatic metabolism via conjugation instead of CYP-mediated oxidation and do not result in active metabolites, making them safer to utilize in patients with significant liver dysfunction. The other benzodiazepines have active metabolites and thus can have a higher risk of causing sedation in patients with liver dysfunction.  In the US, lorazepam is typically the most available of the three options. Dr. Cohen is only switching to lorazepam if someone has severe liver dysfunction, otherwise, he recommends continuing to use diazepam. 

Symptom-triggered vs. fixed-dosing protocols:

Often hospitals will have the option for symptom-triggered vs. fixed-dosing protocols to manage alcohol withdrawal. Making this decision between these two protocol options is often related to the severity of a patient’s alcohol withdrawal. 

Evidence indicates that symptom-triggered protocols may have improved patient outcomes, resulting in shorter hospital stays with fewer benzodiazepine doses needed for patients without significant adverse effects (Mayo-Smith, 1997) (Duby, 2014) (Saitz, 1994). Generally, these protocols are driven by a clinical withdrawal scale such as CIWA or MINDS, and depending on a patient’s score, they are given certain doses of benzodiazepines. This is a good option for patients who are at low risk for severe alcohol withdrawal.

Dr. Cohen also discusses a few options for patients who are at higher risk for severe withdrawal: 

• Front-loading benzos and then transitioning to a fixed or symptom-triggered protocol. (ASAM Clinical Practice Guidelines)

• Utilize a fixed dose protocol until individuals are not requiring symptom-triggered doses in addition to the fixed dosing. Generally, fixed-dose protocols will include additional symptom-triggered doses as needed.

• Phenobarbital can be used for severe alcohol withdrawal (CIWA-Ar >18). Generally, this is started with a loading dose – 10-15 mg/kg split over three doses with a smaller fixed taper dose for the next five days to keep the phenobarbital levels constant. Some institutions are using it as a rescue for patients who have been started on benzodiazepine protocols but are continuing to experience significant withdrawal symptoms. Different hospitals have different policies about where in the hospital you are able to use phenobarbital, making this again a varied practice across the US. Generally, it is most commonly used in the ED, ICU, and step-down settings. The evidence demonstrates that there may be improved patient outcomes (fewer intubations, less ICU time, etc.) with phenobarbital management in comparison to benzodiazepines though additional studies are needed (Askgaard, 2016) (Tidwell, 2018) (Oks, 2020).

Other medication modalities:

• Gabapentin – also increases the concentration of GABA. Mostly used in the outpatient setting but it can be used as an adjunct in the inpatient setting (Murick, 2009).
• Phenobarbital – Acts both as a GABA agonist and a glutamate antagonist. Concerns with phenobarbital include the risk of sedation, as a theoretical risk of hypotension, which is why many hospitals want patients in the ED, SDU, or ICU to administer these loading doses of phenobarbital. See the more detailed discussion above.
• Propofol – used in the ICU setting for intubated patients, does have activity at the GABA receptor (Brotherton, 2016)
• Dexmedetomidine – is used as an adjunct to other GABA-ergic therapies. Dexmedetomidine is an alpha-2 agonist and thus can help to balance some of the excitatory activity (Linn, 2015) 
• Thiamine – In Dr. Cohen’s expert opinion, if someone is admitted and has an IV they should receive IV thiamine supplementation due to the risk of Wenicke’s encephalopathy in patients with AUD.  Dr. Cohen does not discharge people on PO thiamine and instead prefers to focus on medications for the treatment of Alcohol Use Disorder (DeFries, 2021).

Benzodiazepine-resistance alcohol withdrawal: 

A small cohort of patients may not respond as well to benzodiazepines for the treatment of alcohol withdrawal (Hack 2006). For Dr. Cohen, if someone isn’t responding to high doses [variable definition of benzo resistant alcohol withdrawal, some studies consider this threshold to be 50mg of intravenous  diazepam in 1 hour (Hack 2006) of benzodiazepine]), this is when he thinks about switching them over to Phenobarbital. 

Addressing AUD with medications:

It is also vitally important to offer treatment for the underlying cause of all someone’s alcohol withdrawal – Alcohol Use Disorder. It is not always appropriate to discuss this when someone is acutely ill early in their withdrawal syndrome, but as they are nearing the end of their course, it is important to discuss medication options for AUD treatment.  (Curbsiders Addiction Medicine Episode #4). 

Links

1. Whiteout (book)
2. ASAM Pocket Guide for management of alcohol withdrawal (Guide) 
3. Principles of ASAM 

Goal

Listeners will be able to diagnose and manage inpatient alcohol withdrawal with evidence-based medications.

Learning objectives

After listening to this episode listeners will…  

1. Describe the pathophysiology of alcohol withdrawal.
2. Recognize the clinical symptoms and potential complications of alcohol withdrawal
3. Develop an approach to the treatment of inpatient alcohol withdrawal using both symptom-triggered or fixed-dose benzodiazepines. 
4. Describe indications for the choice of one benzodiazepine over another in the treatment of alcohol withdrawal.
5. Describe indications, pathophysiology, and doses for the use of phenobarbital for inpatient alcohol withdrawal.

Disclosures

Dr. Cohen reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Huxley-Reicher, Z, Cohen, S, Roy P, Chan, CA. “#16 Distilling Inpatient Alcohol Withdrawal with Dr. Shawn Cohen”. The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/addiction  August 3rd, 2023