Key Facts

Alcohol withdrawal syndrome (AWS) results from neuroadaptive changes due to chronic alcohol exposure. Abrupt cessation leads to CNS hyperexcitability, autonomic dysfunction, and potentially fatal complications. It is a medical emergency requiring prompt recognition and treatment.

Epidemiology

• 5-10% of patients presenting to Emergency Departments have alcohol-related problems
• ~50% of alcohol-dependent individuals experience clinically significant withdrawal symptoms
• Withdrawal seizures occur in approximately 10% of those with significant withdrawal
• Delirium tremens develops in approximately 5% of those withdrawing; mortality 5-15% untreated
• Risk increases with: previous withdrawal episodes (kindling phenomenon), concurrent illness, older age

Aetiology

• Chronic alcohol use → enhanced GABA-A receptor function (inhibitory) and suppressed NMDA glutamate receptor function (excitatory)
• Compensatory upregulation of excitatory pathways and downregulation of inhibitory pathways during chronic use
• Cessation → sudden loss of GABA enhancement + unopposed excitatory glutamatergic activity
• Kindling: successive withdrawal episodes become progressively more severe due to cumulative neuroadaptation

Pathophysiology

• Autonomic hyperactivity: sympathetic overdrive → tachycardia, hypertension, diaphoresis, pyrexia
• CNS excitability: lowered seizure threshold, tremor, agitation, hallucinations
• Glutamate excitotoxicity: NMDA receptor upregulation leads to calcium influx and neuronal injury
• Electrolyte disturbances: hypomagnesaemia, hypokalaemia, hypophosphataemia exacerbate risk
• Thiamine depletion: impaired thiamine absorption and utilisation increases risk of Wernicke encephalopathy

Mild Withdrawal (6-12 hours)

• Tremor: fine bilateral hand tremor, often the earliest sign
• Anxiety and agitation: restlessness, irritability
• Insomnia: sleep disturbance, vivid dreams
• Nausea and vomiting
• Diaphoresis: sweating, particularly nocturnal
• Mild tachycardia and hypertension

Moderate Withdrawal (12-48 hours)

• Worsening tremor: coarse, visible at rest
• Alcoholic hallucinosis: typically visual (insects, animals), but also auditory and tactile; patient retains intact sensorium (distinguishing from delirium tremens)
• Withdrawal seizures: 12-48 hours post-cessation; generalised tonic-clonic; usually brief and self-limiting; may be recurrent (cluster seizures in ~60%)
• Autonomic instability: marked tachycardia (>100 bpm), hypertension, pyrexia

Severe Withdrawal — Delirium Tremens (48-72 hours, peak day 5)

• Delirium: acute confusion with fluctuating consciousness
• Visual hallucinations: vivid, often terrifying (Lilliputian hallucinations are classical)
• Severe autonomic instability: tachycardia, hypertension, hyperthermia, profuse diaphoresis
• Psychomotor agitation: extreme restlessness, picking at bedclothes
• Coarse tremor
• Risk of cardiovascular collapse: arrhythmias, myocardial ischaemia

Red Flags

• Temperature >38.5°C: suggests delirium tremens or concurrent sepsis
• CIWA-Ar score >20: severe withdrawal requiring aggressive treatment
• Seizures: risk of status epilepticus; do not use phenytoin (ineffective for alcohol withdrawal seizures)
• Chest pain or new arrhythmia: risk of alcohol-related cardiomyopathy, Takotsubo
• Head injury: consider subdural haematoma in confused alcoholic patient
• Hypoglycaemia: must check glucose; give thiamine before glucose

Bedside

• CIWA-Ar score: monitor every 1-2 hours in acute withdrawal; 10 items scored 0-7 each (max 67)
  • <10: mild withdrawal
  • 10-18: moderate withdrawal

  • 18-20: severe withdrawal

• Observations: HR, BP, temperature, RR, SpO2 — at least hourly in acute withdrawal
• Capillary blood glucose: essential before giving IV glucose
• GCS/AVPU: monitor conscious level
• ECG: arrhythmia, prolonged QTc, electrolyte effects

Bloods

• FBC: macrocytosis (raised MCV), thrombocytopenia
• U&Es: hyponatraemia, hypokalaemia, hypomagnesaemia
• LFTs: raised GGT, AST > ALT, deranged synthetic function (albumin, INR)
• Magnesium: commonly low; contributes to seizure risk
• Phosphate: refeeding risk assessment
• Calcium: may be low
• CRP: exclude concurrent infection
• Blood cultures: if pyrexial — sepsis can mimic and co-exist with withdrawal
• Clotting screen: coagulopathy suggests significant liver disease
• Blood alcohol level: useful to guide timing of withdrawal onset

Imaging

• CT head: if seizures are atypical (focal), first presentation, or head injury suspected
• Chest X-ray: if pyrexial — aspiration pneumonia common in heavy drinkers

Special Tests

• Lumbar puncture: if meningism present and CT normal
• EEG: if status epilepticus or non-convulsive seizures suspected
• MRI brain: if Wernicke encephalopathy suspected (mammillary body and periaqueductal changes)

Non-pharmacological

• Calm, well-lit environment: reduce sensory stimulation; maintain orientation
• 1:1 nursing: for severe withdrawal or delirium tremens
• Fluid and electrolyte replacement: IV fluids if unable to take oral; correct hypokalaemia and hypomagnesaemia
• Nutritional support: regular meals; refeeding risk assessment using NICE CG32 criteria
• Thromboprophylaxis: immobile patients at risk of VTE

Pharmacological

• Benzodiazepines (first-line — NICE CG115):
  • Chlordiazepoxide: standard UK choice for managed withdrawal
    • Mild dependence: 10-20 mg QDS, reducing over 5-7 days
    • Moderate dependence: 20-30 mg QDS, reducing over 7-10 days
    • Severe dependence: 40-50 mg QDS, reducing over 7-10 days
  • Lorazepam 1-2 mg IV/IM: preferred in severe liver disease (no active metabolites, glucuronidation)
  • Diazepam: alternative; longer-acting; symptom-triggered regimens in some units
• Thiamine (critical — must precede glucose):
  • IV Pabrinex: 2 pairs (IV ampoules) TDS for 3-5 days, then oral thiamine 100 mg TDS
  • Indications for IV Pabrinex: malnourished, unwell, vomiting, suspected Wernicke, previous withdrawal complications
• Electrolyte replacement:
  • IV magnesium sulphate 20 mmol over 4 hours if hypomagnesaemic
  • IV potassium chloride per local protocol
• Seizure management:
  • Lorazepam 4 mg IV for acute withdrawal seizure
  • Do NOT use phenytoin — ineffective for alcohol withdrawal seizures
  • Recurrent seizures: repeat lorazepam; consider ITU if status epilepticus
• Delirium tremens:
  • High-dose benzodiazepines: lorazepam 2-4 mg IV repeated every 10-15 minutes as required
  • Consider ITU admission if refractory or significant organ dysfunction
  • Haloperidol 2.5-5 mg IM: adjunctive for severe agitation/hallucinations only after adequate benzodiazepine loading (risk of lowering seizure threshold)

Surgical

• Not applicable to acute alcohol withdrawal management

Referral Criteria

• Inpatient detoxification: SADQ >30, previous DTs or withdrawal seizures, significant co-morbidity, homelessness
• ITU/HDU: delirium tremens refractory to treatment, haemodynamic instability, respiratory compromise
• Community alcohol team: for ongoing support after acute withdrawal
• Psychiatry: co-morbid mental illness, suicidal ideation

Mortality

• Untreated delirium tremens: mortality 5-15%
• Treated delirium tremens: mortality <1-2% with appropriate benzodiazepine therapy and supportive care
• Withdrawal seizures: self-limiting in most cases; <3% progress to status epilepticus
• Overall in-hospital mortality for alcohol withdrawal: ~1-5% depending on severity and co-morbidities

Complications

• Aspiration pneumonia: reduced consciousness + vomiting
• Rhabdomyolysis: prolonged seizures, immobility, agitation
• Wernicke encephalopathy: if thiamine not given promptly; ~80% progress to Korsakoff if untreated
• Cardiac arrhythmias: electrolyte disturbances + sympathetic overdrive
• Subdural haematoma: unwitnessed falls during withdrawal
• Kindling: each withdrawal episode increases severity of subsequent episodes; cumulative brain injury
• Prolonged cognitive impairment: may take weeks to months to resolve fully after severe withdrawal

CIWA-Ar Scoring Summary

Chlordiazepoxide Reducing Regimen (Moderate Dependence Example)

Timeline of Alcohol Withdrawal