Alcohol withdrawal symptoms

Alcohol withdrawal is the syndrome of autonomic hyperactivity, tremor, anxiety, insomnia, perceptual disturbance, seizures and delirium that follows stopping or reducing heavy and prolonged alcohol use. It ranges from mild tremor and anxiety to delirium tremens, which has a mortality of 1% to 5% with treatment and up to 35% without.

Definitions. Alcohol withdrawal syndrome requires cessation or marked reduction of heavy and prolonged use. Within hours to days there are 2 or more of the following:

• autonomic hyperactivity (sweating or pulse over 100 beats/min)
• increased hand tremor
• insomnia
• nausea or vomiting
• transient hallucinations or illusions
• psychomotor agitation
• anxiety
• generalised tonic clonic seizures

Delirium tremens is delirium with disturbed attention and consciousness, disorientation, hallucinations (often visual), and severe autonomic hyperactivity. Alcoholic hallucinosis is isolated hallucinations (often auditory) with clear consciousness.

Classification and timeline (after last drink)

• Minor withdrawal, 6 to 24 hours (may start while blood alcohol is still elevated): tremor, anxiety, sweating, nausea, insomnia, headache, palpitations.
• Alcoholic hallucinosis, 12 to 48 hours: visual, auditory or tactile hallucinations with clear consciousness and normal vital signs.
• Withdrawal seizures, 6 to 48 hours (peak 24 hours): generalised tonic clonic, usually single or brief clusters; 3% to 5% of untreated patients, and 30% of these progress to delirium tremens if untreated.
• Delirium tremens, 48 to 96 hours (can start up to 5 to 7 days): confusion, agitation, hallucinations, fever, tachycardia, hypertension, and profuse sweating, lasting 3 to 5 days (rarely up to 2 weeks).
• Protracted withdrawal: insomnia, anxiety, dysphoria and craving for weeks to months.

Epidemiology. Up to half of people with alcohol dependence develop some withdrawal on stopping, and 3% to 5% develop delirium tremens. Admission with alcohol withdrawal is common in general hospitals and about 20% of patients admitted to intensive care have alcohol related problems. Risk of severe withdrawal rises with previous seizures or delirium tremens, daily heavy use for years, concurrent benzodiazepine use, older age, abnormal liver tests, low platelets, low potassium, high blood alcohol on admission, and coexisting acute illness.

Mechanisms. Chronic alcohol enhances inhibitory gamma-aminobutyric acid signalling and suppresses glutamate (N-methyl-D-aspartate) signalling. Sudden removal leaves glutamatergic hyperexcitability and reduced inhibition, with noradrenergic overactivity, causing tremor, autonomic surge, seizures and delirium. Kindling means that repeated withdrawal episodes cause progressively more severe withdrawal.

Key distinctions. Tremor, sweating and anxiety within 24 hours point to withdrawal. Hallucinations with clear consciousness and normal vital signs point to alcoholic hallucinosis.

Fluctuating consciousness, disorientation and severe autonomic signs point to delirium tremens. Confusion with ataxia and ophthalmoplegia point to Wernicke encephalopathy, which can coexist with withdrawal.

Fever and confusion may also be infection, meningitis or hepatic encephalopathy. A first seizure in a patient who drinks needs withdrawal considered, but also head injury, hypoglycaemia, and intracranial lesion.

History

• Alcohol: type, daily quantity (units), pattern and duration of use, time of last drink, age at start, and the amount drunk in the last 24 hours. Use AUDIT and the Severity of Alcohol Dependence Questionnaire.
• Previous withdrawal: tremor, seizures, hallucinations, delirium tremens, and how they were treated. Previous detoxification episodes and number.
• Current symptoms: tremor, sweating, anxiety, insomnia, nausea, vomiting, headache, palpitations, hallucinations, disorientation, and seizures.
• Other substances: benzodiazepines, opioids, stimulants, cannabis, and tobacco, because combined withdrawal is more complex.
• Medical and psychiatric history: liver disease, pancreatitis, epilepsy, head injury, cardiac disease, diabetes, gastrointestinal bleeding, infections, depression, suicide attempts, and psychosis.
• Drugs: anticonvulsants, benzodiazepines, antipsychotics, antidepressants, and interacting medicines.
• Nutrition, vomiting and diarrhoea (dehydration, low magnesium and potassium).
• Social: housing, support, driving, dependants, and readiness to change.
• Collateral history from family or friends.

Examination

• Vital signs: temperature, pulse, blood pressure, respiratory rate, oxygen saturation, and glucose.
• Level of consciousness and orientation, attention (months backwards), hallucinations, and agitation.
• Tremor (outstretched hands), sweating, pupils, and tongue.
• Signs of chronic liver disease (jaundice, ascites, spider naevi, asterixis), pancreatitis, and gastrointestinal bleeding.
• Neurological examination: nystagmus, ophthalmoplegia, ataxia, neuropathy, and focal signs.
• Head and neck for trauma, and chest and abdomen for infection or other illness.
• CIWA-Ar score (10 items: nausea and vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile, auditory and visual disturbances, headache, orientation). The maximum is 67. Under 10 is minimal, 10 to 18 moderate, over 18 severe, and over 15 high risk of seizure or delirium.
• CIWA-Ar requires a communicating patient and cannot be used in delirium.
• Prediction of Alcohol Withdrawal Severity Scale (PAWSS) on admission for risk of complicated withdrawal (4 or more positive items is high risk).

Red flags

• Previous seizures or delirium tremens.
• Seizure now, or confusion, disorientation or hallucinations with agitation.
• Temperature over 38.5 degrees Celsius, pulse over 120 beats/min, or systolic blood pressure over 180 mmHg or under 90 mmHg.
• Wernicke encephalopathy: confusion, ataxia, nystagmus or ophthalmoplegia, hypothermia.
• Head injury with alcohol intoxication or new focal neurological signs.
• Haematemesis, melaena, or jaundice with coagulopathy.
• Suspected infection (pneumonia, spontaneous bacterial peritonitis, meningitis) in a patient with withdrawal.
• Electrolyte disturbance: potassium under 3.0 mmol/L, magnesium under 0.5 mmol/L, sodium under 125 mmol/L, hypoglycaemia, or ketoacidosis.
• Pregnancy.
• Suicidal ideation.
• Blood alcohol over 400 mg/dL with signs of withdrawal, or withdrawal beginning with a high blood alcohol level.
• Co-dependence on benzodiazepines, barbiturates or gamma-hydroxybutyrate.

Special groups

• Older adults: higher risk of delirium, falls and drug sensitivity. Use lower benzodiazepine doses and shorter acting drugs.
• Liver disease: avoid long acting benzodiazepines (chlordiazepoxide, diazepam accumulate) and use lorazepam or oxazepam.
• Pregnancy: admit, give benzodiazepines in lowest effective dose with obstetric and addiction input, and thiamine.
• Critically ill and postoperative patients: withdrawal may start 24 to 72 hours after admission and be mistaken for postoperative delirium.
• Adolescents: rare but possible with heavy dependence.
• Trauma patients: heavy drinking is common; assess for withdrawal on day 2 to 3.
• Region specific: unrecorded and home brewed alcohol (higher alcohol content, methanol risk).

Withdrawal states

• Alcohol withdrawal, mild to moderate.
• Alcoholic hallucinosis.
• Withdrawal seizures.
• Delirium tremens.
• Benzodiazepine, barbiturate or gamma-hydroxybutyrate withdrawal.
• Opioid withdrawal (yawning, rhinorrhoea, diarrhoea, piloerection).

Other causes of tremor, agitation and autonomic hyperactivity

• Sepsis, meningitis, encephalitis, and pneumonia.
• Hypoglycaemia, diabetic ketoacidosis, thyrotoxicosis and thyroid storm.
• Hepatic encephalopathy and uraemia.
• Stimulant intoxication, serotonin syndrome, neuroleptic malignant syndrome, anticholinergic toxicity.
• Hyponatraemia, hypomagnesaemia, hypocalcaemia.
• Pulmonary embolism and hypoxia.
• Phaeochromocytoma and anxiety or panic disorder.

Other causes of confusion and seizure in an alcohol user

• Wernicke encephalopathy and Korsakoff syndrome.
• Intoxication with head injury, subdural haematoma, intracranial haemorrhage, and stroke.
• Epilepsy (alcohol triggers seizures), nonconvulsive status epilepticus, and postictal state.
• Toxic alcohol (methanol, ethylene glycol) and other poisonings.
• Delirium of other cause, psychosis, and mania.
• Pellagra and other nutritional deficiency.
• Alcoholic ketoacidosis and alcohol induced hypoglycaemia.

Coexisting complications

• Alcoholic hepatitis, cirrhosis with variceal bleeding, spontaneous bacterial peritonitis.
• Acute pancreatitis.
• Alcoholic cardiomyopathy and atrial fibrillation (holiday heart).
• Gastritis and Mallory-Weiss tear.
• Rhabdomyolysis.

Step 1. Resuscitate and triage. Check airway, breathing, circulation, glucose, and consciousness. Give thiamine before glucose. Determine severity with CIWA-Ar (or a behavioural scale when the patient cannot communicate) and risk with PAWSS. Decide setting (outpatient, inpatient ward, high dependency or intensive care).

Step 2. First line tests

• Capillary glucose, breath or blood alcohol level, full blood count, urea, creatinine, electrolytes (sodium, potassium), calcium, magnesium, phosphate, liver tests, coagulation (international normalised ratio), amylase or lipase, creatine kinase, and lactate.
• Blood gas if unwell or acidosis suspected (alcoholic ketoacidosis, toxic alcohols).
• ECG (QTc, arrhythmia).
• Urine drug screen and paracetamol level if overdose or co-ingestion is suspected.
• Pregnancy test in women of reproductive age.

Step 3. Targeted tests

• CT head for seizure with head injury, focal signs, anticoagulation, first seizure, or persistent altered consciousness.
• Blood cultures, chest radiograph, urinalysis, and ascitic fluid analysis for infection if febrile.
• Lumbar puncture when meningitis is suspected.
• Electroencephalogram for persisting altered consciousness (nonconvulsive status).
• Serum osmolality, osmolar gap and toxic alcohol levels if anion gap acidosis is unexplained.
• Ammonia is of limited use; clinical diagnosis of hepatic encephalopathy.
• Abdominal ultrasound, endoscopy as needed.
• Thiamine, folate and vitamin B12 levels (do not delay treatment).

Step 4. Interpretation. Tremor, tachycardia and sweating with a falling alcohol level and recent heavy drinking establish withdrawal after exclusion of other causes. A blood alcohol level that is still high does not exclude withdrawal in tolerant patients. Hypokalaemia and hypomagnesaemia lower the seizure threshold and arrhythmia risk and need correction. Persistent fever after 48 hours of delirium tremens treatment should lead to a search for infection.

Limits. CIWA-Ar depends on patient report and is unreliable in delirium, language barriers and intubation. Early signs can be missed in surgical patients. Laboratory tests do not diagnose withdrawal.

Immediate

• Ensure safety: quiet, well lit room, calm approach, frequent orientation, avoiding restraint where possible, and one to one observation for agitated or hallucinating patients.
• Give thiamine before any glucose.
• Preventive dose, all patients in withdrawal: thiamine 200 to 300 mg orally daily (or 100 mg orally three times daily).
• High risk or suspected Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia, malnutrition, hypothermia, or delirium tremens): thiamine 500 mg intravenously over 30 minutes three times daily for 2 to 3 days. Then give 250 mg intravenously or intramuscularly once daily for 3 to 5 days (or until no further improvement), followed by oral thiamine 100 mg three times daily.
• Have resuscitation facilities for anaphylaxis (rare). Give a multivitamin and folic acid 5 mg daily.
• Hypoglycaemia: 10% dextrose 150 to 200 mL intravenously (or 50 mL of 50% dextrose via a large vein) after thiamine.
• Fluids: correct dehydration with oral fluids or intravenous isotonic fluid (0.9% sodium chloride with 5% dextrose for maintenance), with potassium.
• Potassium: potassium chloride to keep the level over 4.0 mmol/L (intravenous 10 to 20 mmol/hour via central access if under 2.5 mmol/L, with monitoring).
• Magnesium: magnesium sulphate 2 g (8 mmol) intravenously over 20 minutes, then 4 to 8 g over 12 to 24 hours for magnesium under 0.7 mmol/L or arrhythmia.
• Phosphate: replace for levels under 0.5 mmol/L (careful with refeeding).

Benzodiazepine regimens (first line)

• Fixed dose (reducing) regimen for mild to moderate withdrawal: chlordiazepoxide 20 to 30 mg orally four times daily on day 1, then 15 to 25 mg four times daily on day 2, then 10 to 20 mg four times daily on day 3, then 5 to 10 mg four times daily on day 4, then 5 to 10 mg twice daily on days 5 to 6, then stop.
• Adjust to symptoms and weight; maximum on day 1 is 200 mg in 24 hours. Dose lower (10 to 20 mg) in older adults or when sedated. Hold a dose if the patient is sedated or breathing slowly.
• Symptom triggered regimen (preferred in monitored settings with trained staff): diazepam 10 to 20 mg orally when CIWA-Ar is 10 or over. Assess every 1 hour while score over 10, then every 4 to 6 hours.
• Repeat every 1 hour until the score falls under 10 (maximum 120 mg in the first 24 hours before senior review). Lorazepam 1 to 4 mg orally every 4 to 6 hours is an alternative.
• Severe withdrawal or delirium tremens: diazepam 10 to 20 mg intravenously (not faster than 5 mg/minute), repeated every 5 to 10 minutes until calm and lightly sedated.
• Large cumulative doses of 100 to 200 mg may be needed in the first hours. Call intensive care when over 200 mg or if breathing is depressed.
• Then maintain with diazepam 5 to 10 mg every 1 to 6 hours as needed (or an infusion in intensive care).
• Lorazepam 1 to 2 mg intravenously or intramuscularly every 15 to 30 minutes is used in liver disease, older adults, and where intravenous access is difficult.
• Benzodiazepine resistant withdrawal (over 50 mg diazepam in 1 hour or over 200 mg in 3 hours): phenobarbital 130 to 260 mg intravenously (or 10 mg/kg over 30 minutes as a loading dose), then 130 mg every 15 to 30 minutes as needed (cumulative 15 mg/kg).
• Alternatively, in intensive care with airway protection: propofol 0.3 to 1.25 mg/kg/hour or dexmedetomidine 0.2 to 1.5 micrograms/kg/hour (dexmedetomidine does not prevent seizures).
• Phenobarbital alone (single loading dose 10 mg/kg intravenously) is an option in selected settings.
• Adjunct drugs for persistent agitation or hallucinations after adequate benzodiazepine: haloperidol 2.5 to 5 mg intravenously or intramuscularly (maximum 20 mg in 24 hours; check QTc and correct potassium and magnesium), or olanzapine 5 to 10 mg.
• Antipsychotics alone are not enough and lower the seizure threshold.
• Beta blockers (propranolol 10 to 40 mg orally twice daily), clonidine 0.1 mg twice daily and dexmedetomidine control autonomic signs. They do not prevent seizures or delirium, and they can mask signs, so use only as adjuncts.
• Carbamazepine 200 mg orally twice daily on days 1 and 2, then 200 mg once daily on days 3 to 5 (or 400 mg daily reducing over 5 days) is an alternative for mild to moderate withdrawal, particularly where benzodiazepine misuse is a concern.
• With carbamazepine, check sodium and liver tests, and avoid in heart block.
• Gabapentin 300 mg three times daily rising to 600 mg three times daily (adjust for renal function) can treat mild withdrawal in outpatients.

Seizure

• Lorazepam 4 mg intravenously (0.1 mg/kg), repeated once after 5 to 10 minutes.
• If the seizure continues beyond 5 minutes give levetiracetam 60 mg/kg (maximum 4.5 g) or phenytoin 20 mg/kg intravenously, and intensive care. Give thiamine and check glucose, sodium, magnesium, calcium.
• Phenytoin does not prevent or treat withdrawal seizures. Long term antiepileptics are not needed for isolated withdrawal seizures.
• Perform CT head after a first seizure or when the pattern is atypical.

Delirium tremens

• Manage in a monitored high dependency or intensive care setting: continuous monitoring of pulse, blood pressure, oxygen saturation and temperature, fluid balance, and glucose every 4 hours.
• Control agitation with intravenous diazepam 10 to 20 mg every 5 to 10 minutes, avoid physical restraint where possible, treat hyperthermia with cooling, and give intravenous fluids (3 to 6 L daily may be needed) and electrolytes. Give nasogastric feeding and thiamine.
• Treat infections, bleeding, pancreatitis, and liver failure.
• Intubate for airway protection when sedation is deep.

Wernicke encephalopathy and Korsakoff syndrome

• Thiamine 500 mg intravenously three times daily for 2 to 3 days, then 250 mg once daily for 3 to 5 days, continued until clinical improvement stops.
• Ensure magnesium is replaced because it is a cofactor.
• Long term thiamine and nutritional support for Korsakoff syndrome, with supervised living.

Outpatient and community withdrawal management

• Suitable if: mild to moderate dependence (under 30 units daily or Severity of Alcohol Dependence Questionnaire under 20), no previous complicated withdrawal, no seizures, no severe psychiatric or physical illness, a reliable carer, a safe home, and a CIWA-Ar under 10.
• Prescribe the reducing chlordiazepoxide regimen (20 to 30 mg four times daily on day 1, falling to 5 to 10 mg twice daily on days 5 to 6) in limited supply (daily or every 2 days collection).
• Also prescribe thiamine 100 mg three times daily, with daily review for the first 3 days, and a carer to observe.

After withdrawal: relapse prevention

• Start naltrexone 50 mg daily or acamprosate 666 mg three times daily as soon as withdrawal ends, with psychological therapy and mutual help groups (second line: baclofen, disulfiram, topiramate, gabapentin).
• Arrange follow up within 1 week, link to addiction services, and treat liver disease.

Special populations

• Pregnancy: admit, use chlordiazepoxide or diazepam at the lowest effective dose or lorazepam in liver disease, give thiamine, and arrange specialist antenatal and neonatal care.
• Older adults: lorazepam 0.5 to 1 mg every 4 to 6 hours, avoid long acting agents, and monitor for oversedation, falls and respiratory depression.
• Liver disease: lorazepam 1 to 2 mg every 4 to 6 hours or oxazepam 15 to 30 mg every 6 hours, with lower doses and slower titration.
• Critically ill: symptom triggered treatment with early phenobarbital or dexmedetomidine as adjunct.
• Kidney impairment: gabapentin and acamprosate need dose reduction.

Monitoring. CIWA-Ar every 1 hour initially, then every 4 to 6 hours; vital signs and sedation score (target calm, awake or easily rousable); fluid balance; glucose; electrolytes daily; liver tests; and QTc with antipsychotics. Watch for oversedation and respiratory depression, especially when using benzodiazepines with phenobarbital.

Referral and escalation. Addiction services for all patients. Intensive care for delirium tremens not controlled with benzodiazepines, refractory seizures, respiratory failure or need for airway protection. Hepatology for alcoholic hepatitis or cirrhosis. Psychiatry for mood disorder and suicide risk. Social work for housing and dependants.

Admission criteria. Previous withdrawal seizures or delirium tremens, current seizure, hallucinations or confusion, CIWA-Ar over 15, PAWSS of 4 or more, pregnancy, severe liver disease, acute illness (pancreatitis, infection, bleeding), unstable electrolytes, malnutrition or suspected Wernicke encephalopathy, older age with frailty, polysubstance dependence, suicidal intent, no safe home or carer, and failed outpatient management.

Discharge and follow up. Discharge when withdrawal scores are under 10 for 24 hours without sedatives, vital signs are normal, and relapse prevention is arranged. Give written advice, thiamine 100 mg three times daily, and limited drug supply. Review in 1 week, then monthly. Safety net advice: return for seizure, confusion, hallucinations, vomiting that prevents medicine intake, persistent tremor and sweating, black stools, vomiting blood, jaundice, or suicidal thoughts.