# Acute Alcohol Withdrawal and Wernicke Encephalopathy

## Introduction

Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition that occurs when a person with chronic heavy alcohol use abruptly reduces or stops drinking. It ranges from mild tremor and anxiety to seizures and delirium tremens (DT). Simultaneously, the internist must recognize and treat Wernicke encephalopathy, a neurologic emergency caused by thiamine deficiency that is frequently underdiagnosed and undertreated.

## Pathophysiology of Alcohol Withdrawal

- Chronic alcohol use enhances **GABA inhibitory activity** and suppresses **NMDA glutamate excitatory activity**
- With abrupt cessation, there is a sudden loss of GABAergic inhibition and unopposed glutamate excitation
- This results in a **hyperadrenergic, hyperexcitable state**: tremor, agitation, autonomic instability, seizures
- Repeated withdrawal episodes lead to **kindling**: progressively worsening withdrawal severity with each episode

## Clinical Spectrum of Alcohol Withdrawal

### Timeline and Stages

| Time After Last Drink | Stage | Manifestations |
|----------------------|-------|----------------|
| 6-12 hours | Minor withdrawal | Tremor, anxiety, insomnia, nausea, diaphoresis, tachycardia |
| 12-24 hours | Alcoholic hallucinosis | Visual/auditory/tactile hallucinations with intact sensorium |
| 24-48 hours | Withdrawal seizures | Generalized tonic-clonic; brief, single or clusters |
| 48-96 hours | Delirium tremens | Altered sensorium, severe autonomic instability, agitation, hallucinations |

- Not all patients progress through all stages; severity depends on drinking history, prior withdrawal, and comorbidities

### Risk Factors for Severe Withdrawal

- Prior history of withdrawal seizures or delirium tremens
- Heavy prolonged alcohol use (> 8 drinks/day)
- Concurrent medical illness, infection, or surgery
- Older age, malnutrition, electrolyte abnormalities
- Elevated BAL on admission or last drink > 24 hours prior

![Timeline of alcohol withdrawal symptom progression from minor symptoms to delirium tremens](/images/residency/alcohol-withdrawal-timeline.jpg)

## Assessment

### CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised)

- Validated 10-item scale assessing: nausea/vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile/auditory/visual disturbances, headache, orientation/clouding of sensorium
- Scored 0-67; guides pharmacotherapy:
  - **< 10**: mild withdrawal; may not require pharmacotherapy
  - **10-18**: moderate withdrawal; pharmacologic treatment indicated
  - **> 18**: severe withdrawal; aggressive treatment required
- Assess every 1-2 hours during active withdrawal
- **Limitations**: requires cooperative patient; unreliable in intubated, delirious, or non-communicative patients

### Alternative Assessment

- **MINDS (Minnesota Detoxification Scale)** or **RASS + clinical judgment** in ICU patients
- In patients who cannot participate in CIWA scoring, use **symptom-triggered assessment** with vital signs and clinical monitoring

## Pharmacologic Management

### Benzodiazepines (First-Line)

- **Symptom-triggered protocol** (preferred): administer benzodiazepines only when CIWA >= 10
  - Reduces total benzodiazepine dose and treatment duration compared to fixed-schedule dosing
  - Diazepam 10-20 mg PO/IV or chlordiazepoxide 50-100 mg PO every 1-2 hours as needed
- **Fixed-schedule protocol**: used when CIWA scoring is unreliable
  - Chlordiazepoxide 50 mg every 6 hours x 4 doses, then 25 mg every 6 hours x 8 doses; taper over 3-5 days
- **Long-acting agents** (diazepam, chlordiazepoxide): preferred; self-tapering pharmacokinetics
- **Short-acting agents** (lorazepam): preferred in hepatic dysfunction (no active metabolites); also preferred in elderly

### Refractory Withdrawal and Delirium Tremens

- Patients requiring > 40 mg diazepam equivalents in the first hour, or escalating doses without improvement
- **Phenobarbital**: 130-260 mg IV; can be added to benzodiazepines or used as primary agent
  - Growing evidence supports phenobarbital as first-line or adjunct in severe withdrawal
- **ICU admission** for hemodynamic monitoring and possible intubation
- **Propofol or dexmedetomidine** infusions for refractory cases requiring ICU-level care
- Avoid antipsychotics as monotherapy (lower seizure threshold); haloperidol can be used adjunctively for hallucinations

### Adjunctive Therapies

- **Thiamine**: 500 mg IV every 8 hours for 3-5 days (see Wernicke section below)
- **Folate**: 1 mg daily
- **Magnesium**: repleet if low; hypomagnesemia is common and predisposes to seizures and arrhythmias
- **Electrolyte monitoring**: potassium, magnesium, phosphorus
- **IV fluids**: for dehydration; monitor for hypoglycemia

![CIWA-Ar-based symptom-triggered benzodiazepine dosing protocol](/images/residency/ciwa-dosing-protocol.jpg)

## Wernicke Encephalopathy

### Pathophysiology

- Caused by **thiamine (vitamin B1) deficiency**
- Thiamine is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase
- Deficiency leads to impaired glucose metabolism and neuronal cell death, particularly in the **mammillary bodies, thalamus, and periaqueductal gray matter**

### Classic Triad (Present in Only ~10-16% of Cases)

- **Encephalopathy**: confusion, apathy, inattention
- **Oculomotor dysfunction**: nystagmus, lateral rectus palsy (CN VI), conjugate gaze palsy
- **Gait ataxia**: wide-based, unsteady gait
- **The full triad is the exception, not the rule**; most patients present with only encephalopathy

### Diagnosis

- **Clinical diagnosis**: do NOT wait for lab confirmation to treat
- MRI may show hyperintensity in mammillary bodies and periaqueductal regions on FLAIR/T2 sequences
- Serum thiamine levels are unreliable and results are often delayed
- Maintain a **low threshold** for treatment in any malnourished, alcohol-dependent, or critically ill patient

### Treatment

- **IV thiamine 500 mg every 8 hours for 3-5 days**, then 250 mg IV daily for 3-5 days, then oral supplementation
- **Must give thiamine BEFORE glucose-containing IV fluids** (glucose metabolism consumes thiamine and can precipitate or worsen Wernicke)
- Oral thiamine is inadequately absorbed in malnourished patients; IV route is essential for treatment
- If untreated, progresses to **Korsakoff syndrome**: irreversible anterograde amnesia and confabulation

![MRI findings in Wernicke encephalopathy showing mammillary body enhancement](/images/residency/wernicke-mri-findings.jpg)

## Discharge Planning

- Screen for alcohol use disorder using AUDIT or AUDIT-C
- Offer **pharmacotherapy for alcohol use disorder**: naltrexone (50 mg PO daily or monthly injection) or acamprosate
- Disulfiram is an alternative but adherence-dependent and requires careful patient selection
- Refer to outpatient addiction treatment, counseling, or mutual support groups
- Continue oral thiamine and folate supplementation

## Key Clinical Pearls

- Use symptom-triggered benzodiazepine dosing (CIWA-based) whenever possible; it reduces total benzodiazepine exposure
- Phenobarbital is an effective adjunct or alternative for severe or refractory withdrawal
- Wernicke encephalopathy is a clinical diagnosis; the classic triad is present in a minority of cases
- Always give IV thiamine before glucose; oral thiamine is insufficient for treatment
- Hospitalization is an opportunity to initiate treatment for alcohol use disorder with naltrexone or acamprosate

## References

1. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. *CNS Drugs*. 2014;28(5):401-410.
2. Hoffman RS, Weinhouse GL. Management of moderate and severe alcohol withdrawal syndromes. *UpToDate*. 2025.
3. Galvin R, Brathen G, Ivashynka A, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. *Eur J Neurol*. 2010;17(12):1408-1418.
4. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. *Cochrane Database Syst Rev*. 2010;(3):CD005063.