Overview
Alcohol Withdrawal
Quick Reference
Critical Alerts
- Give thiamine BEFORE glucose: Prevent Wernicke's encephalopathy
- Delirium tremens mortality: 5-15% if untreated; <1% with treatment
- Benzodiazepines are first-line: Prevent seizures and DTs
- Phenobarbital as adjunct: For refractory cases or benzodiazepine failure
- Cannot reliably predict DTs: Even mild withdrawal can progress
- Hyperadrenergic state can kill: Tachyarrhythmias, MI, aspiration
Key Diagnostics
| Test | Finding | Significance |
|---|---|---|
| Vital signs | Tachycardia, hypertension, fever | Autonomic hyperactivity |
| Fingerstick glucose | Normal or low | Rule out hypoglycemia |
| Electrolytes | Hypokalemia, hypomagnesemia | Common, need replacement |
| Blood alcohol level | May be elevated or zero | Withdrawal can occur at high BAL |
| LFTs | Often elevated | Hepatic dysfunction |
| Ammonia | If encephalopathy suspected | Hepatic encephalopathy |
Emergency Treatments
| Condition | Treatment | Dose |
|---|---|---|
| Thiamine (always first) | IV Thiamine | 500mg IV over 30 min × 3 days (high-dose) |
| Mild-moderate withdrawal | Diazepam or Lorazepam | 10-20mg IV/PO q1-4h as needed |
| Severe withdrawal/DTs | Diazepam boluses | 10-20mg IV q10-15min until controlled |
| Refractory withdrawal | Phenobarbital | 130-260mg IV q15-30min |
| Seizure prophylaxis | Benzodiazepines (not phenytoin) | Adequate dosing prevents seizures |
Definition
Overview
Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition that occurs when individuals with chronic heavy alcohol use abruptly reduce or discontinue drinking. It manifests along a spectrum from mild anxiety and tremor to severe complications including seizures and delirium tremens (DTs).
Classification
Stages of Alcohol Withdrawal:
| Stage | Timing (after last drink) | Features |
|---|---|---|
| Minor withdrawal | 6-24 hours | Anxiety, tremor, insomnia, diaphoresis, tachycardia |
| Alcoholic hallucinosis | 12-48 hours | Visual/auditory/tactile hallucinations with clear sensorium |
| Withdrawal seizures | 6-48 hours (peak 24h) | Generalized tonic-clonic seizures |
| Delirium tremens | 48-96 hours (peak 72h) | Delirium, agitation, autonomic instability, hallucinations |
Severity Assessment (CIWA-Ar Score):
| Score Range | Severity | Management |
|---|---|---|
| 0-9 | Mild | Supportive care, may not need pharmacotherapy |
| 10-19 | Moderate | Pharmacotherapy indicated |
| ≥20 | Severe | Aggressive treatment, consider ICU |
Epidemiology
- Prevalence of AUD: 14.5 million adults in US (5.3% of population)
- Hospitalizations: >500,000 hospitalizations annually in US
- Withdrawal incidence: 50% of heavy drinkers experience some withdrawal
- Seizures: 3-5% of untreated withdrawal patients
- DTs: 5-10% of severe withdrawal; 35-50% without treatment
- Mortality: DTs 5-15% untreated; 1-5% with treatment
Etiology and Risk Factors
Mechanism: Chronic alcohol use → GABA-A receptor downregulation + NMDA receptor upregulation → relative CNS excitability when alcohol removed
Risk Factors for Severe Withdrawal/DTs:
- Previous DTs or withdrawal seizures (strongest predictor)
- Older age
- Concurrent acute illness (infection, trauma, surgery)
- Heavy prolonged drinking history
- Elevated BAL at presentation
- Elevated heart rate at presentation
- Electrolyte abnormalities (hypokalemia, hypomagnesemia)
- Thrombocytopenia
- Concurrent benzodiazepine or barbiturate use
Pathophysiology
Neurobiological Mechanism
Chronic Alcohol Effects:
- GABA-A receptors: Alcohol enhances GABA (inhibitory) → chronic use leads to downregulation
- NMDA receptors: Alcohol inhibits glutamate (excitatory) → chronic use leads to upregulation
- Net effect of chronic use: Compensatory CNS adaptation to depressant effects
Withdrawal State:
- Removal of alcohol: Loss of GABA enhancement + unopposed NMDA activity
- CNS hyperexcitability: Seizure threshold lowered, sympathetic activation
- Autonomic hyperactivity: Catecholamine surge → tachycardia, hypertension, hyperthermia
- Duration: Neuroadaptation takes 7-10 days to normalize
Kindling Phenomenon
- Each subsequent withdrawal episode is more severe
- Lower threshold for seizures with repeated withdrawals
- Progressive neuronal sensitization
- Emphasizes importance of adequate treatment
Metabolic Complications
- Hypoglycemia: Impaired gluconeogenesis, poor oral intake
- Hypokalemia: GI losses, renal wasting, alkalosis
- Hypomagnesemia: Renal wasting, poor intake, increased utilization
- Hypophosphatemia: Refeeding, respiratory alkalosis
- Thiamine deficiency: Poor intake, impaired absorption, increased utilization
Clinical Presentation
Symptom Timeline
6-12 Hours Post-Cessation:
12-24 Hours:
24-48 Hours:
48-72 Hours:
Physical Examination
Vital Signs:
General:
| Finding | Significance |
|---|---|
| Tremor | Coarse, symmetric, worse with intentional movement |
| Diaphoresis | Autonomic hyperactivity |
| Mydriasis | Elevated catecholamines |
| Nystagmus | Consider Wernicke's if present |
| Jaundice | Underlying liver disease |
| Spider angiomata | Chronic liver disease |
| Gynecomastia | Chronic alcohol use |
| Asterixis | Hepatic encephalopathy |
Mental Status:
CIWA-Ar Assessment Tool
| Item | Assessment | Score Range |
|---|---|---|
| Nausea/Vomiting | Severity | 0-7 |
| Tremor | Arms extended | 0-7 |
| Paroxysmal sweats | Observation | 0-7 |
| Anxiety | "Do you feel nervous?" | 0-7 |
| Agitation | Observation | 0-7 |
| Tactile disturbances | Hallucinations, itching, burning | 0-7 |
| Auditory disturbances | Hallucinations, sounds | 0-7 |
| Visual disturbances | Hallucinations, photophobia | 0-7 |
| Headache | "Does your head feel full?" | 0-7 |
| Orientation | Person, place, time, date | 0-4 |
| Total | 0-67 |
Anxiety, irritability, restlessness
Common presentation.
Tremor (usually hands)
Common presentation.
Headache
Common presentation.
Diaphoresis
Common presentation.
Anorexia, nausea, vomiting
Common presentation.
Insomnia
Common presentation.
Mild tachycardia, hypertension
Common presentation.
Red Flags
Life-Threatening Conditions
| Finding | Concern | Action |
|---|---|---|
| Fever >8.3°C (101°F) | DTs, infection, aspiration | Aggressive treatment, workup for infection |
| Severe agitation/combativeness | DTs, safety risk | High-dose benzodiazepines, restraints PRN |
| Seizures | Alcohol withdrawal seizures | Control with benzodiazepines; status requires phenobarbital |
| Altered consciousness | DTs, hepatic encephalopathy, other organic | Full workup, ammonia, imaging |
| Autonomic instability | Risk of arrhythmia, cardiovascular collapse | ICU, aggressive treatment |
| Respiratory depression | Over-sedation, aspiration | Airway management, may need intubation |
| Wernicke's triad (confusion, ataxia, ophthalmoplegia) | Wernicke's encephalopathy | High-dose IV thiamine immediately |
High-Risk Features
- Previous DTs or withdrawal seizures
- CIWA score >15 on presentation
- Concurrent medical illness or trauma
- Multiple medical comorbidities
- BAL >200 mg/dL at presentation
- Polysubstance use (especially benzodiazepines)
Differential Diagnosis
Conditions That Mimic or Complicate Alcohol Withdrawal
| Condition | Distinguishing Features | Key Evaluation |
|---|---|---|
| Sepsis/Infection | Fever, hypotension, specific source | WBC, cultures, imaging |
| Meningitis/Encephalitis | Neck stiffness, photophobia | LP, CT/MRI |
| Hepatic encephalopathy | Liver disease, asterixis, elevated ammonia | Ammonia, LFTs |
| Wernicke's encephalopathy | Ophthalmoplegia, ataxia, confusion | Clinical diagnosis, treat empirically |
| Hypoglycemia | Low glucose, rapid improvement with dextrose | Fingerstick glucose |
| Head trauma/ICH | Trauma history, focal signs | CT head |
| Thyrotoxicosis | Thyroid signs, elevated free T4 | TSH, free T4 |
| Anticholinergic toxicity | Dry, mydriatic, flushed, altered | Tox screen, clinical |
| Sympathomimetic toxicity | Drug use history, similar presentation | Urine drug screen |
| Benzodiazepine withdrawal | Similar but usually less severe autonomic | History of benzo use |
| Status epilepticus | Continuous seizures | Clinical, EEG |
Diagnostic Approach
Initial Evaluation
Immediate (All Patients):
- Vital signs with continuous monitoring
- Fingerstick glucose
- Brief neurological examination
- CIWA-Ar score
Laboratory Studies:
| Test | Rationale |
|---|---|
| CBC | Infection, thrombocytopenia (liver disease) |
| CMP | Electrolytes (K, Mg, Phos), glucose, renal function |
| LFTs | Liver disease severity |
| Magnesium | Often low, needs replacement |
| Phosphorus | Refeeding syndrome prevention |
| Lipase | Alcoholic pancreatitis |
| Blood alcohol level | Baseline, can withdraw at any level |
| Ammonia | If hepatic encephalopathy suspected |
| Lactate | If sepsis or hypovolemia suspected |
| Coagulation studies | Liver synthetic function |
| Urine drug screen | Polysubstance use |
Imaging and Other Tests:
| Test | Indication |
|---|---|
| CT head | Altered mental status, trauma, focal signs |
| CXR | Fever, respiratory symptoms, aspiration |
| Lumbar puncture | Fever with altered mental status (rule out meningitis) |
| ECG | Baseline, arrhythmia monitoring |
Risk Stratification
PAWSS (Prediction of Alcohol Withdrawal Severity Scale):
- Used in non-intoxicated patients
- Helps identify who needs pharmacological prophylaxis
High-Risk Indicators:
- Prior complicated withdrawal (DTs, seizures)
- High CIWA on admission
- Active comorbidities
- Prior treatment for alcohol withdrawal
Treatment
Principles of Management
- Supportive care: Calm environment, IV fluids, electrolyte replacement
- Thiamine first: Before any glucose to prevent Wernicke's
- Benzodiazepines: First-line; prevents seizures and DTs
- Symptom-triggered dosing: CIWA-based preferred over fixed schedules
- Adjunct therapies: For specific symptoms as needed
- Treat complications: Seizures, arrhythmias, aspiration
Thiamine Replacement (Critical)
Why Before Glucose: Glucose → increased thiamine utilization → precipitates Wernicke's in deficient patients
Dosing:
| Indication | Dose | Duration |
|---|---|---|
| Prophylaxis (all AWS patients) | 100-250mg IV/IM daily | 3-5 days |
| Suspected or confirmed Wernicke's | 500mg IV TID | 3 days, then 250mg daily |
Benzodiazepine Therapy
Preferred Agents:
| Agent | Route | Half-life | Notes |
|---|---|---|---|
| Diazepam | IV, PO | Long (20-100h) | Preferred if no liver failure; self-tapering |
| Lorazepam | IV, IM, PO | Intermediate (10-20h) | Hepatic impairment; no active metabolites |
| Chlordiazepoxide | PO | Long (30-100h) | Oral only; for mild withdrawal |
Symptom-Triggered Protocol (CIWA-based):
| CIWA Score | Action |
|---|---|
| <10 | Monitor every 4-8 hours; no medication needed |
| 10-19 | Diazepam 10-20mg PO/IV or Lorazepam 2-4mg; reassess in 1 hour |
| ≥20 | Aggressive treatment: Diazepam 20mg IV q10-15min until CIWA <10 |
Fixed-Schedule Protocol (Alternative):
- Used when CIWA assessment unreliable (intubated, cognitively impaired)
- Example: Diazepam 10mg q6h × 4 doses, then 5mg q6h × 8 doses
Severe/Refractory Withdrawal:
- Some patients require massive doses (>500mg diazepam equivalents in 24h)
- Add phenobarbital early if not responding
- Consider intubation if risk of respiratory compromise
Phenobarbital Therapy
Indications:
- Benzodiazepine-resistant withdrawal
- Adjunct to benzodiazepines in severe DTs
- Alternative in "resistant" patients (prior failed treatment)
- Polysubstance users with benzodiazepine tolerance
Dosing:
| Protocol | Dose | Notes |
|---|---|---|
| Adjunctive | 130mg IV q30min PRN (max 10mg/kg) | Added to benzodiazepines |
| Primary (some protocols) | 10mg/kg IV loading dose | Followed by CIWA-based dosing |
Cautions:
- Respiratory depression (especially with benzodiazepines)
- Long half-life (accumulation)
- Monitor sedation closely
Dexmedetomidine (Adjunct in ICU)
Role: Adjunctive agent in ICU for refractory DTs Mechanism: Alpha-2 agonist; reduces sympathetic outflow Advantages: Does not cause respiratory depression Limitations: Does not prevent seizures; must use with benzodiazepines
Electrolyte Replacement
| Electrolyte | Typical Replacement | Monitoring |
|---|---|---|
| Magnesium | 2-4g MgSO4 IV if low | Recheck in 6-8 hours |
| Potassium | 10-40 mEq/h IV (based on level) | Recheck frequently |
| Phosphorus | 15-30 mmol IV if low | Especially if refeeding |
Nutrition
- NPO if agitated, seizing, or aspiration risk
- Early enteral nutrition when safe
- Multivitamin daily
- Folic acid 1mg daily
- Monitor for refeeding syndrome
Seizure Management
Withdrawal Seizures:
- Usually self-limited, single or brief cluster
- Treat with benzodiazepines (not phenytoin - ineffective for AWS seizures)
- Diazepam 10-20mg IV or Lorazepam 4mg IV
- Most will not recur if adequately treated
Status Epilepticus:
- Treat per status protocol
- Phenobarbital preferred second-line (GABAergic)
- Phenytoin NOT effective for alcohol withdrawal seizures
Disposition
Admission Criteria
ICU Admission:
- Delirium tremens
- Status epilepticus
- Severe autonomic instability
- Respiratory compromise
- Requiring phenobarbital infusion
- Benzodiazepine dosing >200mg diazepam equivalents
Floor/Step-Down Admission:
- Moderate withdrawal (CIWA 10-19) requiring treatment
- History of severe withdrawal with current mild symptoms
- Concurrent medical illness
- Significant electrolyte abnormalities
- Social factors precluding safe discharge
Discharge Criteria
- CIWA consistently <10 for 24+ hours
- Vitally stable without medication for 24 hours
- Ambulating safely
- Tolerating oral intake
- Electrolytes normalized
- No concurrent acute illness
- Safe disposition plan
- Substance abuse treatment arranged
Follow-Up Recommendations
| Timeframe | Purpose |
|---|---|
| 24-48 hours | PCP or addiction medicine if early discharge |
| 1-2 weeks | Addiction medicine/psychiatry |
| Ongoing | AA, outpatient treatment program, counseling |
| 1 month | Evaluate for medication-assisted treatment (naltrexone, acamprosate) |
Patient Education
Condition Explanation
- "Your body has become used to alcohol, and when you stop drinking, your brain becomes overactive."
- "This can cause shaking, sweating, fast heart rate, and in severe cases, seizures or dangerous confusion."
- "We will give you medication to help your brain calm down safely while the alcohol clears your system."
Safety Information
- "Alcohol withdrawal can be dangerous - never stop drinking suddenly if you've been drinking heavily."
- "Seek medical help before trying to quit if you drink daily or heavily."
- "Withdrawal symptoms usually peak around 48-72 hours and improve over 5-7 days."
Resources and Support
- Alcoholics Anonymous (AA)
- SAMHSA National Helpline: 1-800-662-4357
- Outpatient detox programs
- Inpatient rehabilitation options
- Community support groups
Warning Signs Requiring Return
- Fever
- Uncontrollable shaking
- Seizures
- Confusion or hallucinations
- Inability to keep medications or fluids down
- Chest pain or palpitations
Special Populations
Elderly
- Higher risk of complications
- More likely to have concurrent medical illness
- More sensitive to benzodiazepines - start lower doses
- Longer duration of withdrawal possible
- Higher mortality from DTs
Pregnant Patients
- Benzodiazepines can be used (untreated withdrawal is more dangerous)
- Risk of fetal alcohol syndrome from continued drinking
- Fetal monitoring if viable gestation
- Obstetric involvement essential
- Addiciton medicine referral for ongoing care
Patients with Liver Disease
- Use lorazepam, oxazepam (no hepatic metabolism)
- Watch for hepatic encephalopathy (mimics DTs)
- Check ammonia if altered mental status
- Higher risk of bleeding, coagulopathy
- Lower protein diet if encephalopathic
Patients with History of Severe Withdrawal
- Higher risk of recurrent DTs and seizures
- Lower threshold for admission
- Consider prophylactic treatment
- Phenobarbital may be preferred
Polysubstance Users
- May have concurrent benzodiazepine or opioid dependence
- Watch for multiple withdrawal syndromes
- May need higher benzodiazepine doses (cross-tolerance)
- Phenobarbital useful adjunct
Quality Metrics
Performance Indicators
| Metric | Target | Rationale |
|---|---|---|
| Thiamine before glucose | 100% | Prevent Wernicke's |
| CIWA assessment documented | 100% | Guide treatment |
| Benzodiazepine administered if CIWA ≥10 | 100% | Prevent progression |
| Electrolytes checked and repleted | 100% | Common deficiencies |
| Addiction medicine referral | >0% | Long-term recovery |
| Readmission rate (30 day) | <15% | Adequate treatment, follow-up |
Documentation Requirements
- Alcohol use history (amount, frequency, last drink)
- Previous withdrawal history (seizures, DTs)
- CIWA scores at regular intervals
- Benzodiazepine doses and timing
- Clinical response to treatment
- Complications encountered
- Discharge plan including addiction treatment
Key Clinical Pearls
Diagnostic Pearls
- Withdrawal can occur at any BAL: Even with elevated blood alcohol
- DTs can appear at 48-96 hours: Monitor admitted patients closely
- Hallucinations ≠ DTs: Alcoholic hallucinosis has clear sensorium; DTs has delirium
- Previous DTs = high risk of recurrence: Most important predictor
- Check for other causes: Fever, infection, head injury, other intoxications
- Wernicke's is clinical diagnosis: Triad present in only 10-15%
Treatment Pearls
- Thiamine BEFORE glucose: Always, in all patients
- Benzodiazepines prevent DTs and seizures: Phenytoin does NOT
- Symptom-triggered is preferred: Less medication, shorter treatment
- Don't underdose: Some patients need hundreds of mg of diazepam
- Add phenobarbital early if not responding: Don't wait for failure
- Long-acting benzos (diazepam) self-taper: Smoother course
Disposition Pearls
- 24-hour symptom-free before discharge: Ensures stability
- Arrange addiction treatment BEFORE discharge: Window of opportunity
- Don't discharge to homelessness: High risk of immediate relapse
- Medication-assisted treatment exists: Naltrexone, acamprosate, disulfiram
- This is a chronic disease: Frame as such for patient and family
References
- Hoffman RS, Weinhouse GL. Management of moderate and severe alcohol withdrawal syndromes. UpToDate. 2024.
- Mayo-Smith MF. Pharmacological management of alcohol withdrawal: A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-151.
- Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014;371(22):2109-2113.
- Long D, et al. Comparison of the CIWA-Ar with the RASS for assessment of alcohol withdrawal syndrome in ICU patients. Crit Care Med. 2018;46(1):e6-e10.
- 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.
- Liang Y, et al. Dexmedetomidine for alcohol withdrawal syndrome: A systematic review and meta-analysis. Front Pharmacol. 2020;11:614812.
- Day E, et al. Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev. 2013;(7):CD004033.
- ASAM. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020;14(3S):1-72.