Management of Inpatient Alcohol Withdrawal

Full update September 2022

This FAQ addresses common questions about the pharmacotherapy of alcohol withdrawal in acute care patients.

Question

Answer/Pertinent Information

When and how are benzodiazepines used in the treatment of alcohol withdrawal?

  • Benzodiazepines are the medications of choice for treatment of alcohol withdrawal because they treat symptoms and prevent progression to serious complications (e.g., seizures, delirium).2
  • There is no consensus on the best protocol, but symptom-triggered therapy is the preferred dosing method.2,10
    • Benefits include faster time to symptom control, lower total benzodiazepine dose, reduced need for and shorter duration of mechanical ventilation, reduced need for ICU admission, and shorter length of ICU stay.3
    • A benzodiazepine is given PO or IV every 1 to 2 hrs based on a symptom score (e.g., CIWA-Ar score) until significant clinical improvement occurs (e.g., CIWA-Ar ≤10) or the patient becomes oversedated.1
      • Protocols may have different doses for different scores (e.g., chlordiazepoxide 50 mg for CIWA-Ar 10 to 18; chlordiazepoxide 100 mg for CIWA-Ar ≥19).2
  • Patients with severe withdrawal (e.g., CIWA-Ar score ≥19) may initially need high doses (i.e., front-loading).2
    • Examples: diazepam 20 mg or chlordiazepoxide 50 to 100 mg every 1 to 2 hrs until CIWA-Ar <10 or patient is sedated.1,2
  • Patients with a history of withdrawal seizures should receive scheduled doses (e.g., diazepam 20 mg every six hours for three days, plus additional doses based on the symptom score).1

Are certain benzodiazepines preferred for alcohol withdrawal management?

  • There is no evidence that one benzodiazepine is more effective than another.1
  • The most commonly used benzodiazepines are chlordiazepoxide, diazepam, and lorazepam.1,2 Many prescribers prefer chlordiazepoxide or diazepam because their long half-lives offer less frequent dosing, steady serum levels, and a self-tapering effect.1 Diazepam and chlordiazepoxide are preferred for “front-loading” (see above).2
    • Chlordiazepoxide (PO) has a slow onset of action (up to 3 hours), but is long-acting (24 to 48 hrs).5,8
      • PO route eases transition to discharge.8 Potentially less abuse for outpatients.5
    • Diazepam has a long duration of action (>20 to 50 hrs) and quick onset (1 to 5 min for IV route).5,8
      • Use with caution in kidney impairment; it has an active metabolite that is eliminated via the kidney.4
      • Avoid IM administration due to unpredictable absorption.1
    • Lorazepam is shorter-acting and has no active metabolites, and so is preferred in the elderly or those with severe liver impairment.1,2,4
      • Onset of action for IV lorazepam is 5 to 20 minutes, with ~6 to 10 hrs duration of action.4,8
  • Use a parenteral agent when fast onset is required or the patient cannot cooperate with PO intake (e.g., seizures, hallucinations, CIW-Ar score >19).
  • Approximate equivalents: diazepam 10 mg equates to lorazepam 1.5 mg, IV midazolam 3 mg, or
    chlordiazepoxide 25 mg.7,15,18

What are some common scoring tools used to assess alcohol withdrawal?

  • CIWA-Ar is a 10-item symptom assessment scale appropriate for use in any care setting with well-established reliability and validity.1
  • RASS is a one-item sedation and agitation assessment scale (range -5 to +4) appropriate for use in medical and surgical settings with reliability and validity in patients who are awake or sedated and/or ventilated.1
  • MINDS is increasingly used in the ICU setting.14 It is quicker to use than the CIWA-Ar but is not validated.2

What is the role of phenobarbital in alcohol withdrawal?

  • While benzodiazepine efficacy is GABA-dependent, phenobarbital is GABA-independent. Because of their different mechanisms of action, phenobarbital can work synergistically with benzodiazepines, or may be effective when benzodiazepines are not.3
  • Phenobarbital has multiple administration routes (i.e., PO, IV, IM), a defined therapeutic range, a long half-life, and auto tapers (i.e., may not need discharge medication).8,9,12
  • Potential disadvantages of phenobarbital include higher risk of drug interactions, and potential for dose stacking if given more frequently than every 20 to 40 minutes.8,17
  • There is no proof that phenobarbital is superior to benzodiazepines for treatment of alcohol withdrawal.8 Most data come from the ICU setting vs ED setting, and is retrospective.8,13Potential roles for phenobarbital include:
    • patients in whom benzodiazepines cannot be used (see footnote b).2
    • severe or resistant withdrawala in ICU patients, as a benzodiazepine adjunct.2
    • prophylaxis of alcohol withdrawal in high-risk patients (see prophylaxis section, below, for more information).2,6,8,9
  • Reserve parenteral phenobarbital for experienced prescribers in a closely monitored settings (e.g., ED, ICU).2
  • Dosing:
    • Most patients can be controlled with a cumulative dose of 20 mg/kg IBW in about 48 hours. At this point, consider other causes, or need for adjuncts. Consider a “hard stop” max cumulative dose of 30 mg/kg IBW in about 48 hours (correlates to upper level of therapeutic range).16
    • Consider RASS target of 0 to -1.11
    • A front-loading strategy in the ED may reduce need for ICU admission.2
    • Dosing examples:
      • For patients taking opioids, who have already received a significant benzodiazepine dose, or who have severe liver impairment (avoid in hepatic encephalopathy): 130 mg IV q 30 to 60 min as needed.6,16 Skip the loading dose.16,19
      • Front-loading strategy: 10 mg/kg (IBW) IV in 100 mL of normal saline over 30 minutes.2,16 Can follow with additional doses of 130 to 260 mg q 15 to 30 minutes if needed.8,16
      • Fixed dose: 260 mg x 1 IV, then 130 mg IV q 15 to 30 min.2
      • Escalating dose (after maximizing benzodiazepine): 60 mg, then 120 mg in 30 min., then 240 mg in
        30 minutes.2

What is the role of propofol in alcohol withdrawal?

Propofol

  • Can use as a benzodiazepine alternative or adjunct (for resistant withdrawala) for patients receiving mechanical ventilation.2,14
  • Consider dosing as for ICU sedation.8

What are the options if a benzodiazepine cannot be used (see footnote b)?

Phenobarbital

  • See above.

Propofol

  • See above.

Carbamazepine

  • Can be continued post-discharge for ongoing treatment of alcohol use disorder.2
    • Decreases alcohol craving and consumption.2
    • May be less sedating and safer in combination with alcohol than benzodiazepines.2
  • 600 to 800 mg/day. Taper to 200 to 400 mg over four to nine days.2

Gabapentin

  • Can be continued post-discharge for ongoing treatment of alcohol use disorder but note abuse potential.2
    • Decreases alcohol craving and consumption.2
    • May be less sedating and safer in combination with alcohol than benzodiazepines.2
  • 1,200 mg x 1, then 600 mg q 6 hrs on day 1, then 1,200 mg/day for one to three days, then taper to 300 to 600 mg/day over four to seven days. Additional doses as needed.2

What are the options for resistant withdrawal?a

Phenobarbital

  • Phenobarbital is the benzodiazepine alternative with the most evidence and is most often used.14 See phenobarbital section above for details.

Dexmedetomidine

  • Consider for resistant withdrawal in ICU patients, as a benzodiazepine adjunct.2 Don’t use alone; it does not prevent seizures.2
  • Target symptoms: tachycardia, hypertension, anxiety, and agitation.2
  • May reduce benzodiazepine requirement, sedation, and delirium, but might increase length of stay.2,8
  • Monitor for bradycardia and hypotension.2,3

Propofol

  • Reserve for patients receiving mechanical ventilation.2
  • Less bradycardia but more hypotension than dexmededtomidine.2
  • Consider dosing as for ICU sedation.8

What other adjuncts are used in the treatment of alcohol withdrawal?

  • Ensure adequate benzodiazepine dosing before using an adjunct.2
  • Beta-blockers can be used to control tachycardia or hypertension.2
  • Clonidine can be used to control tachycardia, hypertension, and anxiety.1,2
  • Carbamazepine, gabapentin, or valproic acid can be used if the patient does not have liver disease and is not of childbearing potential.2 Note that carbamazepine or gabapentin can also be used as monotherapy (see above).
    • carbamazepine: 200 mg q 8 hrs or 400 mg q 12 hrs2
    • gabapentin: 400 mg q 6 to 8 hrs2
    • valproic acid: 300 to 500 mg q 6 to 8 hrs2
  • Ketamine is increasingly used, but data are limted.8,14
  • For delirium, consult your institution’s delirium protocol.2See our toolbox, Preventing and Treating Delirium in Inpatients.

Should at-risk inpatients receive prophylaxis for alcohol withdrawal syndrome?

  • Only retrospective data is available.8
  • Experts advocate for prophylaxis in patients with suspected alcohol dependence who are at risk of severe or complicated withdrawal (e.g., acutely ill patients, patients with a history of alcohol withdrawal, patients with severe coronary artery disease).2,8
  • A front-loaded regimen (see above) is recommended, or at least a single dose for patients with lower risk.2
  • Benzodiazepines are preferred.2
  • Phenobarbital is the recommended alternative.2
    • One protocol uses IM phenobarbital at a total dose of 6 to 15 mg/kg IBW on day 1, with the dose based on the risk of alcohol withdrawal and sedation.6,9 Forty percent of the calculated dose is given immediately, 30% is given three hours later, and 30% is given three hours after the second dose.9 The patient is switched to PO phenobarbital on day 2, then tapered.9

Which vitamins and electrolytes should be supplemented in alcohol withdrawal?

  • Thiamine 100 mg once daily (IV or IM preferred initially) for three to five days started as soon as the diagnosis of alcohol withdrawal is reasonably certain, before any glucose-containing fluid is given, to prevent Wernicke-Korsakoff syndrome.1,2 If Wernicke encephalopathy is suspected, give thiamine 500 mg IV every eight hours.2
  • Multivitamin replacement is recommended.1
    • Patients may be deficient in pyridoxine, folate, vitamin B12, calcium, zinc, iron, vitamin A, and vitamin E.1
  • Consider folic acid 1 mg daily for ICU patients and patients with suspected Wernicke encephalopathy.2
  • Replace electrolytes (e.g., magnesium, phosphorus, potassium) if needed.2 However, magnesium is not recommended to prevent or treat alcohol withdrawal due to lack of evidence.2

What are some drugs that are NOT recommended for the treatment of alcohol withdrawal?

  • Alcohol2
  • Baclofen (insufficient evidence)2
  1. Resistant alcohol withdrawal (also called benzodiazepine-resistant alcohol withdrawal, treatment-resistant alcohol withdrawal, or refractory alcohol withdrawal) is sometimes described as uncontrolled symptoms after administration of diazepam 120 to 200 mg or lorazepam 30 to 40 mg within the first three to four hours.2
  2. Benzodiazepines should be avoided in some patients. see Figure 4-3 of the SAMHSA Detoxification and Substance Abuse Treatment protocol at https://store.samhsa.gov/sites/default/files/d7/priv/sma15-4131.pdf.

Abbreviations: CIWA-Ar = Clinical Institute Withdrawal Assessment of Alcohol Scale, revised; ED = emergency department; GABA = gamma-aminobutyric acid; IBW = ideal body weight; ICU = intensive care unit; IM = intramuscular; IV = intravenous; PO = oral; q = every; MINDS = Minnesota Detoxification Scale ; RASS = Richmond Agitation-Sedation Scale; SAMHSA = Substance Abuse and Mental Health Services Administration.

References

  1. Substance Abuse and Mental Health Services Administration. Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45. HHS Publication No. (SMA) 15-4131. Rockville, MD: Center for Substance Abuse Treatment, 2006. (Revised 2015). https://store.samhsa.gov/sites/default/files/d7/priv/sma15-4131.pdf. (Accessed August 10, 2022).
  2. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020 May/Jun;14(3S Suppl 1):1-72. Erratum in: J Addict Med. 2020 Sep/Oct;14(5):e280.
  3. Ferreira JA, Wieruszewski PM, Cunningham DW, et al. Approach to the Complicated Alcohol Withdrawal Patient. J Intensive Care Med. 2017 Jan;32(1):3-14.
  4. Clinical Pharmacology powered by Clinical Key. Tampa, FL: Elsevier; 2022. http://www.clinicalkey.com. (Accessed August 12, 2022).
  5. Angelini MC. Substance use disorders. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2018:1874-1902.
  6. Nisavic M, Nejad SH, Isenberg BM, et al. Use of Phenobarbital in Alcohol Withdrawal Management - A Retrospective Comparison Study of Phenobarbital and Benzodiazepines for Acute Alcohol Withdrawal Management in General Medical Patients. Psychosomatics. 2019 Sep-Oct;60(5):458-467.
  7. Bostwick JR, Gardner KN. Anxiety disorders. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: the Clinical Use of Drugs. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2018:1731-61.
  8. Yanta J, Swartzentruber G, Pizon A. Alcohol withdrawal syndrome: improving outcomes in the emergency department with aggressive management strategies. Emerg Med Pract. 2021 Mar 15;23(Suppl 3):1-41.
  9. Nisavic M. Inpatient management of alcohol withdrawal. https://mghcme.org/app/uploads/2021/02/Nisavic-Alcohol-Withdrawl-1.pdf#. (Accessed August 12, 2022).
  10. Dixit D, Endicott J, Burry L, et al. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy. 2016 Jul;36(7):797-822.
  11. Oks M, Cleven KL, Healy L, et al. The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit. J Intensive Care Med. 2020 Sep;35(9):844-850 [abstract].
  12. Hendey GW, Dery RA, Barnes RL, et al. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. 2011 May;29(4):382-5.
  13. Koh JJ, Malczewska M, Doyle-Waters MM, Moe J. Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review. BMC Emerg Med. 2021 Nov 6;21(1):131. Erratum in: BMC Emerg Med. 2022 Jan 31;22(1):17.
  14. Cucci MD, Palm N, Vazquez D, et al. Survey of critical care practices for alcohol withdrawal syndrome in the intensive care unit. J Am Coll Clin Pharm 2022;1-9.
  15. Barr J, Zomorodi K, Bertaccini EJ, et al. A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001 Aug;95(2):286-98.
  16. Farkas J. Alcohol withdrawal. The Internet Book of Critical Care. https://emcrit.org/ibcc/etoh/#phenobarbital_guideline. (Accessed August 13, 2022).
  17. Tidwell WP, Thomas TL, Pouliot JD, et al. Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol. Am J Crit Care. 2018 Nov;27(6):454-460.
  18. e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2022. Benzodiazepines. CPhA monograph (May 2015). http://www.e-therapeutics.ca. (Accessed August 25, 2022).
  19. Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013 Mar;44(3):592-598.

Cite this document as follows: Clinical Resource, Management of Inpatient Alcohol Withdrawal. Hospital Pharmacist’s Letter/Pharmacy Technician’s Letter.September 2022. [380919]




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