Alcohol withdrawal

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 w/ 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

Diagnosis

CIWA score

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

  • Headache 0-7
  • Orientation 0-4
  • 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)
  • 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]

Alpha-2 agonists (Dexmedetomidine)

  • Decrease severity of sxs, 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)

Ketamine

  • May have some use in refractory cases
  • Blocks the NMDA receptor which is excited an unregulated. [2]

Nutritional supplementation

  • Banana bag
    • Thiamine 100mg IV
    • Folate 1mg IV (cheaper PO)
    • MVI 1 tab IV (cheaper PO)
    • Magnesium sulfate 2mg IV
    • Normal saline as needed for hydration

Outpatient Management

Don’t use phenytoin or fosphenytoin to treat seizures caused by drug toxicity or drug withdrawal.[3]

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[4]
    • Some protocols call for higher dosing - 600 or 800mg x1
  • Similar efficacy to lorazepam in decreasing craving and anxiety[5]
  • Example regimens (please use discretion and balance risk/benefits with your own clinical judgment)

Example outpatient lorazepam taper

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

Example outpatient gabapentin taper

Similar in efficacy to lorazepam according to one RCT[6]

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

Special Situations

  • The propylene glycol diluent in lorazepam, phenobarbital and diazepam, may induce a hyperosmolar anion gap metabolic acidosis if given as a drip in high doses ≥ 48hrs.[7] Consider alternatives such as propofol or dexmedetomidine if patients need long term sedation for Delirum tremens

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

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. 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
  3. 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/
  4. 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.
  5. 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
  6. 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/
  7. 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.
  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/