Alcohol Withdrawal Syndrome

MADISON HEATH, PHARMD

COLUMBUS REGIONAL HEALTH
MARCH 27, 2023

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 • Understand how alcohol withdrawal occurs in patients
Objectives • Recognize when certain strategies of mitigating alcohol
withdrawal symptoms may be necessary
• Apply principles of alcohol withdrawal syndrome (AWS)
management to a patient

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 Pathophysiology
• Alcohol = CNS Depressant
• Enhances Inhibitory Portion (GABA)
• Inhibits Excitatory Portion (Glutamate Receptors)

• Alcohol dependence requires constant alcohol for homeostasis

• Abrupt Stop = Over activation of CNS, Results in symptoms of
alcohol withdrawal syndrome (AWS)

https://emcrit.org/ibcc/etoh/

NEWMAN RK, STOBART GALLAGHER MA, GOMEZ AE. ALCOHOL WITHDRAWAL.

IN: STATPEARLS. STATPEARLS PUBLISHING; 2022. ACCESSED MARCH 13, 2023 3
HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK441882/?REPORT=CLASSIC
Signs and Symptoms of Withdrawal
Minor
• Hypertension, Insomnia, Hyperreflexia, Tremors, Anxiety, GI Upset, Headache, Palpitations
• ~6 hours after cessation

Moderate
• Hallucinations, Seizures
• ~12-24 hours after cessation

Severe
• Delirium Tremens

NEWMAN RK, STOBART GALLAGHER MA, GOMEZ AE. ALCOHOL WITHDRAWAL.

IN: STATPEARLS. STATPEARLS PUBLISHING; 2022. ACCESSED MARCH 13, 2023 4
HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK441882/?REPORT=CLASSIC
Delirium Tremens (DTs)
• Most severe symptom
• “Altered sensorium with significant autonomic dysfunction and vital sign abnormalities”
• Encompasses hallucinations, tachycardia, hypertension, hyperthermia, agitation and sweating
• Can last up to ~7 days

NEWMAN RK, STOBART GALLAGHER MA, GOMEZ AE. ALCOHOL WITHDRAWAL.

IN: STATPEARLS. STATPEARLS PUBLISHING; 2022. ACCESSED MARCH 13, 2023 5
HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK441882/?REPORT=CLASSIC
Risk Factors for Severe Withdrawal
Associated with increased risk:
• History of alcohol withdrawal delirium or alcohol withdrawal seizure
• Numerous prior withdrawal episodes
• Comorbid medical or surgical illness
• >65 years old
• Long duration of heavy and regular alcohol consumption
• Seizure(s) during the current withdrawal episode
• Marked autonomic hyperactivity on presentation
• Psychological dependence on GABAergic agents – BZDs/Barbiturates
May increase risk:
• Concomitant use of other addictive substances
• Positive blood alcohol concentration in with signs and symptoms of withdrawal
• Signs and symptoms of a co-occurring psychiatric disorder are active and reflect a moderate level of severity

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 6
Monitoring Scales
• Risk Assessment
• Alcohol Use Disorders Identification Test – Piccinelli Consumption: AUDIT-PC
• Prediction of Alcohol Withdrawal Severity Scale: PAWSS
• Symptom Assessment
• Clinical Institute Withdrawal Assessment for Alcohol Revised: CIWA-Ar
• Designed to measure severity of alcohol withdrawal for research studies
• Limitations: Clinician training required, time to administer, requires patient to self-report
symptoms
• Confusion Assessment Method for ICU Patients (CAM-ICU), Richmond Agitation-Sedation
Scale (RASS): Preferred in patients experiencing delirium

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 7
 AUDIT - PC
0-7 = Sensible Drinking

8-15 = Hazardous Drinking

16-19 = Harmful Drinking

20+ = Possible Dependence

HTTPS://WWW.SCIENCEDIRECT.COM/TOPICS/MEDICINE-AND-DENTISTRY/CAGE-QUESTIONNAIRE 8
 PAWSS
≥4 = High Risk for Moderate to Severe
AWS

HTTPS://WWW.THE-HOSPITALIST.ORG/HOSPITALIST/ARTICLE/121823/SHOULD-
PATIENT-WHO-REQUESTS-ALCOHOL-DETOXIFICATION-BE-ADMITTED-OR-TREATED/2/

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CIWA-Ar
<10 = Mild

10 – 19 = Moderate

≥18 = Severe

HTTPS://WWW.CFP.CA/CONTENT/CFP/63/9/691.FULL.PDF 10
 Management Strategies
Mild Moderate Severe
CIWA-Ar <10 CIWA-Ar 10-18 CIWA-Ar ≥19
• Pharmacotherapy or Supportive • Pharmacotherapy • Pharmacotherapy
Care • 1st Line: BZDs • 1st Line: BZDs
• BZDs, Carbamazepine, • Alt: Carbamazepine, • Alt: Phenobarbital
Gabapentin Gabapentin or Phenobarbital
• Alt: Carbamazepine, • Adjunct: Carbamazepine,
Gabapentin or Phenobarbital Gabapentin or Valproic Acid
• Adjunct: Carbamazepine,
Gabapentin or Valproic Acid

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 11
Management Strategies
• Add GABA
• BZDs, Gabapentin, Carbamazepine, Valproic Acid

• Increase GABA Sensitivity

• Phenobarbital

• Supportive Therapy

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Regimen Types
• Front-Loading Therapy
• Recommended for patients at high-risk of severe withdrawal
• Also appropriate for patients not at high-risk but have one of the following:
• History of Severe/Complicated Withdrawal
• Acute Medical, Psychiatric or Surgical Illness
• Sign/Symptoms of Withdrawal and a positive blood alcohol content
• Shown to reduce duration of treatment, withdrawal seizure incidents and duration of delirium
•Symptom-Triggered Therapy
• Based on a symptom scale - CIWA

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 13
 Benzodiazepines
• 1st line for moderate and severe AWS
• Effect at preventing seizures and delirium
•Longer Acting > Shorter Acting
• Dosing:
• Preferred: Symptom-triggered treatment
• Front loading: Preferred for pts with severe alcohol withdrawal
• Agents: Diazepam and Chlordiazepoxide
• Fixed dosing with taper
•Monitoring: Signs of over-sedation and respiratory depression

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 14
Carbamazepine, Gabapentin and Valproic Acid

Carbamazepine Gabapentin Valproic Acid

Increase in availability of
Structurally related to GABA
GABAergic activity GABA/Enhance action of GABA

Favorable for AWS when also to be

used for treating Alcohol Use Adjunct to BZD therapy
Alternative if BZDs are Disorder
contraindicated
Alternative if BZDs are Contraindicated in liver disease and
contraindicated pts with childbearing potential

Adjunct to BZD therapy Insufficient evidence on

Adjunct to BZD therapy
monotherapy for AWS treatment

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 15
Phenobarbital
• Alternative to BZDs for pts at risk of/with severe alcohol withdrawal
• MOA: Increases duration of channel opening when bound to GABA  ↑ hyperpolariza on of
neuron thereby increasing the sedative effects of GABA
• Direct block on glutamate signaling

• Adverse Effects: Bradycardia, Bradypnea, Hypothermia, Hypotension, Pulmonary Edema, AKI,

Stevens-Johnson Syndrome
• T1/2: ~79 hours

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020.
LEXICOMP ONLINE. WALTHAM, MA: WOLTERS KLUWER HEALTH, INC. HTTP://ONLINE.LEXI.COM. ACCESSED MARCH 15, 2023. 16
CRH Phenobarbital Policy
• Concern for respiratory depression*?
• Yes: 10mg/kg based on IBW over 30 minutes
• No: 15mg/kg based on IBW over 30 minutes
• Redose – if CIWA still elevated (>9)
• 3mg/kg Q4H x 1-2 doses
• Max cumulative dose: 21mg/kg IBW in 24hours
• Maintenance Dosing:
• Oral dose starting on day 2 can be considered
• 1 mg/kg orally twice a day for 48 hours (round dose to nearest 16.2 mg)
• Do Not prescribe maintenance dose to patients with hepatic dysfunction or cirrhosis
*Factors for concern include opioid administration, previous benzodiazepines in last 12 hours, head
injury, age >65 years old, and hepatic dysfunction

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CRH Phenobarbital Policy
• CIWA Monitoring
• > 10: Reassess every hour
• 6-10: Reassess every 2 hours
• 0-5: Reassess every 2 hours X2 then every 4 hours
• Every 4 hours: Respiratory Rate, Heart Rate, Blood Pressure
• Serum Level: Drawn ~4 hours after loading dose
• Target serum level 15 mcg/mL
• Stop additional dose if level is >20mcg/mL
• Toxicity general only occurs at levels > 40 mcg/mL

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Resistant Alcohol Withdrawal
Experience severe/complicated withdrawal despite high dosed BZDs

Propofol
• Can be used in pts already requiring mechanical ventilation

Dexmedetomidine

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 19
Other Agents
Alpha 2 Adrenergic Blockers
• Ex. Clonidine and Dexmedetomidine
• Can be adjunct to control autonomic hyperactivity and
anxiety

Beta Blockers
• Can be adjunct for persistent hypertension or tachycardia

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 20
Monitoring
Vital Signs, Hydration, Orientation, Sleep, Emotional Status, Over-Sedation and Respiratory
Depression

Moderate – Severe Withdrawal/Requiring Pharmacotherapy: Every 1-4 Hours x24h

• Stabilized: Extended to every 4-8 Hours x24h

Mild Withdrawal and Low Risk of Complicated Withdrawal: Observed up to 36h

Alcohol Withdrawal Seizure: Every 1-2 Hours x6-24h

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 21
Supportive Care
Thiamine IV or IM, 100mg daily x3-5days
Hypomagnesemia, Cardiac Arrhythmias, Electrolyte
Magnesium Disturbances, History of EtOH withdrawal seizures

Phosphorous Replenished if <1 mg/dL

Folate 1mg daily

Multivitamin

ALVANZO A, KLEINSCHMIDT K, KMIEC JA ET AL. THE ASAM CLINICAL PRACTICE

GUIDELINE ON ALCOHOL WITHDRAWAL MANAGEMENT. J ADDICT MED. 2020. 22
Patient Case
MM is a 42yo M who arrives to the ED experiencing N/V and persistent sweating. This is the 3rd
time this year he’s presented with similar symptoms. Upon talking with MM, you discover he is
hearing voices and won’t stop trying to get out of bed. He knows he’s in the hospital because he
“asked to get dropped off here.” You ask him what the date is and he says “sometime this week.”
His last drink was 8 hours ago. He has since been transferred to the floor and has started to
experience tremors.

BP 146/78 BAL 250mg/dL

Mg 1.0 Phos 1.2

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Patient Case
• What are some risk factors that MM has?
• What is his CIWA score?
• Would MM be a candidate for front-loading therapy?
• What agent(s) would be the best option for MM?
• Supportive care measures?

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 Patient Case
• What are some risk factors that MM has?
• Numerous prior withdrawal episodes
• Long duration of heavy and regular consumption
• Marked autonomic hyperactivity on presentation
• Positive BAL

• What is his CIWA score?

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• N/V = 4; Tremor = 2; Sweats = 4; Anxiety = 4; Agitation = 4; Tactile Disturbances = 0; Auditory Disturbances = 3; Visual
Disturbances = 0; Headache = 0; Orientation = 3
• Would MM be a candidate for front-loading therapy?
• Yes, he is at a severe level with a CIWA >19.

• What agent(s) would be the best option for MM?

• BZDs or Phenobarbital
• Supportive care measures?
• Thiamine IV, Folic Acid 1mg daily and MVI daily. Replenish Magnesium.

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References
• Alvanzo A, Kleinschmidt K, Kmiec JA et al. The ASAM Clinical Practice Guideline on Alcohol
Withdrawal Management. J Addict Med. 2020.
• Lexicomp Online. Waltham, MA: Wolters Kluwer Health, Inc. http://online.lexi.com. Accessed
March 15, 2023.
• Newman RK, Stobart Gallagher MA, Gomez AE. Alcohol Withdrawal. In: StatPearls. StatPearls
Publishing; 2022. Accessed March 13, 2023
https://www.ncbi.nlm.nih.gov/books/NBK441882/?report=classic

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Alcohol Withdrawal Syndrome
MADISON HEATH, PHARMD
COLUMBUS REGIONAL HEALTH
MARCH 27, 2023

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