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)

Ketamine

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

Nutritional supplementation

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

  • 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[6]

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

  • Consider discharge with 3 day course of benzodiazepines if patients are attempting to quit alcohol
  • Consider possible exclusions for outpatient treatment[8]:
    • 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. 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/