Alcohol Withdrawal Syndrome

Alcohol withdrawal syndrome is the group of symptoms that develops when a person who is physically dependent on alcohol stops or sharply reduces intake. It ranges from mild tremor and anxiety to seizures and delirium tremens, a life threatening emergency.

• Chronic alcohol use enhances inhibitory GABA-A signalling and suppresses glutamate (NMDA) activity; abrupt cessation leaves the nervous system hyperexcitable with raised autonomic and noradrenergic activity.
• Timeline from the last drink:
  • 6 to 24 hours: minor withdrawal (tremor, sweating, anxiety, insomnia, nausea, palpitations).
  • 12 to 48 hours: withdrawal seizures (generalised tonic clonic, usually brief and single or a short cluster) and alcoholic hallucinosis (visual or tactile hallucinations with clear consciousness).
  • 48 to 96 hours: delirium tremens (disorientation, agitation, fluctuating consciousness, hallucinations, fever, tachycardia, hypertension, profuse sweating), mortality of about 1 to 5 percent when treated and up to 15 to 35 percent when untreated.
• Risk factors for severe withdrawal: previous seizures or delirium tremens, heavy daily drinking (over 8 to 10 units daily for years), previous detoxifications, older age, concurrent illness (infection, pancreatitis, hepatic disease), electrolyte disturbance (low magnesium, potassium, sodium), low platelets, use of benzodiazepines or other sedatives, and head injury.
• Wernicke encephalopathy (confusion, ophthalmoplegia or nystagmus, ataxia) from thiamine deficiency commonly coexists and must be treated.

• Mild: coarse tremor of hands, tongue and eyelids; sweating; anxiety; agitation; insomnia; nausea and vomiting; headache; tachycardia; hypertension; craving.
• Moderate: marked agitation, visual and tactile distortions, severe tremor, vomiting.
• Seizures: single or multiple generalised seizures.
• Delirium tremens: global confusion, vivid visual hallucinations (often small animals), delusions, extreme agitation, fever above 38 degrees Celsius, heart rate over 120/min, blood pressure instability, dehydration.
• Complications: aspiration, arrhythmia, hypoglycaemia, rhabdomyolysis, hepatic decompensation, upper gastrointestinal bleeding, pancreatitis, and Wernicke-Korsakoff syndrome.
• History: quantity and pattern of drinking, time of last drink, previous withdrawal, seizures, other substances, liver disease, head injury, psychiatric illness, medicines.
• Examination: vital signs, hydration, tremor, consciousness, orientation, eye movements, gait, liver stigmata, signs of bleeding or infection, and capillary glucose.

• Clinical, by the pattern of symptoms soon after stopping alcohol.
• Severity scoring: the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar, 10 items, maximum 67): below 10 mild, 10 to 15 moderate, over 15 severe, over 20 high risk of seizures and delirium tremens. Repeat hourly to every 4 hours during treatment.
• Breath alcohol level where available; capillary glucose at once.
• Blood tests: FBC with MCV, urea and electrolytes, magnesium, phosphate, calcium, liver function and gamma glutamyl transferase, clotting, amylase or lipase if abdominal pain, creatine kinase, blood cultures if febrile, ethanol level and urine drug screen.
• ECG (QT prolongation, arrhythmia); chest X-ray if hypoxia or fever; CT head for seizures with focal signs, head injury, or persistent decreased consciousness.
• Differentials: sepsis, hypoglycaemia, intracranial haemorrhage or trauma, meningitis, hepatic encephalopathy, thyrotoxicosis, withdrawal from benzodiazepines, barbiturates or opioids, stimulant intoxication, serotonin syndrome, non-convulsive status epilepticus.

Decide the setting

• Outpatient (supervised daily review) only if CIWA-Ar is under 10, no history of seizures or delirium tremens, no serious medical or psychiatric illness, a responsible adult is present, the patient can take oral medicines, and the patient is not pregnant.
• Admit for CIWA-Ar of 10 or more, previous complicated withdrawal, seizures, hallucinations, delirium, significant comorbidity, Wernicke features, age over 65, failed outpatient withdrawal, malnutrition, or poor home support. Admit to intensive care for delirium tremens, seizures not controlled, or unstable vital signs.

Thiamine (give before any glucose containing fluid)

• Prevention in all patients: thiamine 100 mg orally three times daily (or 200 mg intramuscularly or intravenously daily for 3 days if at risk, malnourished, or vomiting).
• Suspected Wernicke encephalopathy: thiamine 500 mg intravenously (in 100 mL of normal saline over 30 minutes) three times daily for 3 days, then 250 mg daily intravenously or intramuscularly for 3 to 5 more days or until no further improvement, followed by 100 mg orally daily. Keep resuscitation equipment ready for the rare anaphylaxis.
• Add oral multivitamin, folic acid 5 mg daily, and pyridoxine.

Benzodiazepines (the cornerstone)

• Fixed dose regimen (mild to moderate, outpatient or ward): chlordiazepoxide 20 to 30 mg orally four times daily on day 1, reducing the daily dose by 20 percent each day to stop over 5 to 7 days; extra 10 to 20 mg as needed for breakthrough symptoms. Avoid in liver impairment.
• Symptom triggered regimen (inpatient): diazepam 10 to 20 mg orally every 1 to 2 hours while CIWA-Ar is 10 or more until it falls under 8, then monitor; or chlordiazepoxide 50 to 100 mg orally each hour.
• Liver failure, older adults, severe lung disease: lorazepam 1 to 2 mg orally, intramuscularly or intravenously every 4 to 6 hours, or oxazepam 15 to 30 mg orally every 6 hours, because of shorter half life and no active metabolites.
• Seizure: lorazepam 4 mg intravenously (repeat after 10 minutes) or diazepam 10 mg intravenously slowly (maximum 20 mg); do not use phenytoin or other antiepileptics for withdrawal seizures, which are not effective; seek other causes with CT if focal.
• Delirium tremens: diazepam 10 to 20 mg intravenously every 5 to 10 minutes until calm and lightly sedated; large cumulative doses may be needed, with airway equipment and monitoring (oxygen saturation, blood pressure, ECG). If resistant to high dose benzodiazepines, phenobarbital 130 to 260 mg intravenously then 130 mg every 15 to 30 minutes, or propofol or dexmedetomidine in intensive care (with ventilation).
• Haloperidol 2.5 to 5 mg orally or intramuscularly every 8 to 12 hours may be added only for hallucinations or agitation despite adequate benzodiazepine, with ECG monitoring; it lowers the seizure threshold.

Supportive care

• Quiet, well lit room, reorientation, avoid restraints; vital signs every 1 to 4 hours.
• Fluids: oral rehydration if possible; intravenous 0.9 percent sodium chloride with dextrose after thiamine; avoid fluid overload.
• Correct electrolytes: potassium (keep above 4.0 mmol/L), magnesium (magnesium sulfate 2 g intravenously over 1 to 2 hours if low, then oral replacement), phosphate (oral or intravenous according to level).
• Antipyretics for fever; antibiotics for infection; proton pump inhibitor for gastritis; monitor for pancreatitis and gastrointestinal bleeding.
• Avoid driving or operating machinery during treatment.

After withdrawal: relapse prevention

• Psychosocial treatment (motivational interviewing, cognitive behavioural therapy, mutual help groups, family therapy) for all.
• Acamprosate 666 mg orally three times daily (333 mg three times daily if creatinine clearance is 30 to 50 mL/min; contraindicated below 30 mL/min), starting as soon as abstinent, for 6 to 12 months.
• Naltrexone 25 mg orally for 1 to 3 days then 50 mg daily for 3 to 12 months; contraindicated with opioid use or acute hepatitis or liver failure; check liver enzymes at baseline and monthly for 3 months.
• Disulfiram 200 mg orally daily (supervised) for motivated patients without cardiac, liver or psychotic disease; warn about a severe reaction with any alcohol including that in food, medicines and mouthwash.
• Baclofen 5 mg three times daily increasing to 10 mg three times daily (specialist; useful in liver disease); topiramate 25 mg at night increasing to 100 mg twice daily; gabapentin 300 mg increasing to 300 to 600 mg three times daily (misuse potential).
• Continue thiamine 100 mg orally daily.

Follow up

• Review within 1 week of discharge and monthly; check liver function, FBC, and vitamin levels; screen for depression, anxiety and suicidality; offer hepatitis B and C screening, and vaccinations.

Special groups

• Pregnancy: inpatient withdrawal with diazepam or lorazepam under obstetric supervision; give thiamine and folic acid 5 mg; fetal alcohol spectrum disorder prevention is the aim; avoid disulfiram and topiramate.
• Liver disease: use lorazepam or oxazepam at reduced doses; avoid naltrexone in acute liver failure; baclofen is an alternative for relapse prevention.
• Older adults: lower starting doses of lorazepam (0.5 to 1 mg), higher risk of falls, delirium, and prolonged confusion.
• Epilepsy or head injury: high risk, so admit.