Alcohol withdrawal seizures

Background

  • Generalized tonic-clonic seizures occurring in the context of alcohol withdrawal
  • Onset: 6-48 hours after last drink (peak at 24 hours)
  • Multiple seizures occur in ~60% of patients
  • ~33% progress to delirium tremens if untreated
  • May occur as isolated finding or as part of the broader alcohol withdrawal spectrum
  • Key pearl: First-time seizure in a chronic alcoholic still requires full workup — do not assume alcohol withdrawal without ruling out other causes

Clinical Features

  • Brief, generalized tonic-clonic seizures (usually <5 minutes)
  • Typically self-limited
  • Focal seizure features or prolonged seizure suggest an alternative or concurrent etiology (intracranial hemorrhage, CNS infection, structural lesion)
  • Post-ictal period may be brief

Differential Diagnosis

Ethanol related disease processes

Seizure

Evaluation

  • Do not anchor on withdrawal — rule out other causes especially in first-time seizures:
    • Glucose, BMP (electrolytes, magnesium), CBC
    • CT head: obtain if first seizure, focal findings, prolonged altered mental status, head trauma, or anticoagulation
    • Consider LP if fever or meningeal signs
  • Assess CIWA score to guide withdrawal severity


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
  • Ethanol level, urine toxicology screen
  • Magnesium and phosphate levels (commonly depleted in alcoholics)

Management

  • Benzodiazepines are first-line for both acute seizure treatment and withdrawal prophylaxis:
    • Lorazepam 2-4 mg IV for active seizure
    • Diazepam 10-20 mg IV for active seizure (faster onset, longer acting)
  • Do NOT use phenytoin or fosphenytoin for alcohol withdrawal seizures (ineffective and potentially harmful)
  • Replete electrolytes: magnesium (2g IV), thiamine (100-500 mg IV BEFORE glucose), folate

Benzodiazepine overview

Agents Equivalent PO dose (mg) Route Onset of Action (min) Half Life (hr) Metabolism
Chlordiazepoxide 25 PO, IV 30 - 120 7-28 CYP; active metabolites
Diazepam 5 PO, IV, IM 2 - 5 20-120 CYP; active metabolites
Lorazepam 1 PO, IM, IV 15-20 8-19 Glucuronidation

Benzodiazepines

  • Diazepam (Valium) 5-10 mg IV (depending on severity)
    • May repeat q5-10 min for severe withdrawal (may increase dose by 10 mg every 5-10 min until desired effect achieved, max dose of 200 mg)
    • Half-life 20-100 h (long acting)
  • Lorazepam (Ativan) 1-4mg IV (depending on severity)
    • May repeat q15-20 min for severe withdrawal (titrated to effect)
    • Rarely causes hepatitis, as opposed to diazepam which may cause a cholestatic hepatitis[1]
    • Half-life 10-20 h (medium acting)

Other Agents

For use in cases refractory to benzodiazepine treatment

  • Propofol
    • If patient does not respond to high doses of benzodiazepines
    • 0.3-1.25 mg/kg up to 4 mg/kg/hr (consider intubation), for up to 48 hours
  • Barbiturates (Phenobarbital)
    • Used when refractory to benzodiazepines (consider after patient has received equivalent of 200 mg diazepam)
      • Phenobarbital 130-260 mg 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]
  • α-2 agonists (Dexmedetomidine)
    • Decrease severity of symptoms, but only supplemental to GABA-ergic first-lines
    • Dexmedetomidine drip, start 0.2 mcg/kg/hr, likely needing no more than 0.7 mcg/kg/hr[3]
  • Ketamine
    • May have some use in refractory cases
    • Blocks the NMDA receptor which is excited an unregulated. [4]

Special Situations

Disposition

  • Admit for observation and monitored benzodiazepine protocol
  • ICU if: status epilepticus, refractory seizures, concern for delirium tremens, hemodynamic instability
  • Consider outpatient management only if: isolated seizure, no other concerning features, reliable follow-up, safe discharge plan

See Also

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. ↑ Rayner SG, et al. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012; 2: 12. Published online 2012 May 23. doi: 10.1186/2110-5820-2-12.
  4. ↑ 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
  5. ↑ 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.
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