Alcohol withdrawal

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Background

  • Withdrawal symptoms due to reduced GABA and increased glutamate
  • Benzos useful due to cross tolerance at ethanol GABA receptor
  • Symptom triggered therapy
    • As effective as fixed dose therapy, but with more rapid detox

Clinical Features

  • Reduction in alcohol use that has been heavy and prolonged
  • At least 2 of the following
    • Autonomic hyperactivity (e.g., diaphoresis, HR>100)
    • Increased hand tremor
    • Insomnia
    • Nausea/vomiting
    • Transient visual, tactile, or auditory hallucinations
    • Psychomotor agitation
    • Anxiety
    • Grand mal seizures

Seizures

  • Onset after last drink: 6-48h
  • Multiple seizures: 60% of patients
  • Progression to DTs: 33% of patients
  • Treat with benzos (not phenytoin)

Alcoholic Hallucinosis

  • Onset after last drink: 12-24hr
  • Visual hallucinations are most common
  • Different from delirium tremens
    • Resolves within 24-48 from last drink (before onset of DTs)
    • No delirium
    • Normal vital signs

Differential Diagnosis

Ethanol related disease processes

Sedative/hypnotic withdrawal

Seizure

Evaluation

CIWA score

Clinical Institute Withdrawal Assessment – Alcohol – revised (CIWA-Ar)

  • Headache 0-7
  • Orientation 0-3
  • Tremor 0-7
  • Sweating 0-7
  • Anxiety 0-7
  • Nausea (and Vomiting) 0-7
  • Tactile Hallucinations 0-7
  • Auditory Hallucinations 0-7
  • Visual Hallucinations 0-7
  • Agitation 0-7

Maximum Score = 67

  • <8: Typically do not require medication
  • 8-19: Medication
  • ≥20: Medication and admission

Inpatient Management

Start aggressive Benodiazepine therapy at CIWA score of 8. Consider ICU admission with score >20

Benzodiazepines

  • Diazepam (Valium) 5-10mg IV (depending on severity)
    • May repeat q5-10min for severe withdrawal (double dose until desired effect achieved)
    • Half-life 20-100h (long acting)
  • Lorazepam (Ativan) 1-4mg IV (depending on severity)
    • May repeat q15-20min for severe withdrawal (titrated to effect)
    • Rarely causes hepatitis, as opposed to diazepam which may cause a cholestatic hepatitis[1]
    • Half-life 10-20h (medium acting)

Alpha-2 agonists (Dexmedetomidine)

  • Decrease severity of symptoms, but only supplemental to GABA-ergic first-lines
  • Dexmedetomidine drip, start 0.2 mcg/kg/min, likely needing no more than 0.7 mcg/kg/min

Barbituates (Phenobarbital)

  • Used when refractory to benzodiazepines
  • Phenobarbital 130-260mg IV q 15-20 minutes
  • Can also be used as a first line load at 10 mg/kg prior to giving benzodiazepines to decrease benzodiazepine requirements and ICU admissions [2]

Ketamine

  • May have some use in refractory cases
  • Blocks the NMDA receptor which is excited an unregulated. [3]

Nutritional supplementation

Special Situations

Outpatient Management

Don’t use phenytoin or fosphenytoin to treat seizures caused by drug toxicity or drug withdrawal.[5]

Chlordiazepoxide

Generally for outpatient treatment of mild cases and as a taper

  • 25-50mg of chlordiazepoxide is equivalent to 10mg of diazepam
  • 50mg of chlordiazepoxide every 8 hours for two days, then decrease to 25mg every 8 hours for another two days followed by 25mg PRN as needed.

Anticonvulsants^

  • Gabapentin 400mg PO TID[6]
    • Some protocols call for higher dosing - 600 or 800mg x1
  • Similar efficacy to lorazepam in decreasing craving and anxiety[7]

^These are example regimens (use discretion and balance risk/benefits with your own clinical judgment)

Example outpatient lorazepam taper

  • 2mg tid x3 days
  • 2mg bid on day 4
  • 2mg once on day 5

Example outpatient gabapentin taper

Similar in efficacy to lorazepam according to one RCT[8]

  • 400mg tid x3 days
  • 300mg bid on day 4
  • 300mg once on day 5

Disposition

Admit

  • Multiple seizures
  • DTs
  • Decreased LOC
  • Inability to control withdrawal after administrating 3-4 doses of benzo's
  • Consider ICU admission with CIWA score >20

Discharge

  • Consider discharge with 3 day course of benzodiazepines if patients are attempting to quit alcohol
  • Consider possible exclusions for outpatient treatment[9]:
    • Substance use disorders except alcohol, nicotine, or cannabis
    • Major Axis I psych disorder
    • Medication history of benzodiazepines, beta-blockers, calcium-channel blockers, antipsychotics
    • History of head injury, epilepsy, medical instability, ECG abnormality, grossly abnormal lab value

See Also

External Links

References

  1. ↑ National Institute of Diabetes and Digestive and Kidney Diseases. Lorazepam Drug Record. http://livertox.nih.gov/Lorazepam.htm
  2. ↑ Rosenson J, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013; 44(3):592-598.
  3. ↑ Wong, A et al. Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother. 2015 Jan;49(1):14-9. PMID: 25325907
  4. ↑ Arroliga AC, Shehab N, McCarthy K, Gonzales JP. Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults*. Critical Care Medicine. 2004;32(8):1709–1714. doi:10.1097/01.CCM.0000134831.40466.39.
  5. ↑ Choosing Wisely. American College of Medical Toxicology and The American Academy of Clinical Toxicology. http://www.choosingwisely.org/clinician-lists/acmt-and-aact-phenytoin-or-fosphenytoin-to-treat-seizures/
  6. ↑ Leung JG, Hall-Flavin D, Nelson S, et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015; 49(8):897-906.
  7. ↑ Myrick, H et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 2009 Sep;33(9):1582-8. PMID: 19485969
  8. ↑ Myrick et al. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL. Alcohol Clin Exp Res. 2009 Sep; 33(9): 1582–1588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769515/
  9. ↑ Myrick et al. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL. Alcohol Clin Exp Res. 2009 Sep; 33(9): 1582–1588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769515/
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