11.5 Alcohol Use Disorder & Withdrawal

Substance use disorders and psychiatric toxic emergencies constitute high-acuity medical scenarios encountered across inpatient wards, emergency departments, and intensive care units. Mastery of withdrawal timelines, targeted pharmacotherapies, antidote administration, and comprehensive suicide risk stratification is paramount for the ABIM Internal Medicine examination.

1. Alcohol Use Disorder (AUD): Screening & Withdrawal Syndrome

Clinical Screening & Risk Assessment

• AUDIT-C (Alcohol Use Disorders Identification Test-Consumption): Highly sensitive 3-question screen evaluating drinking frequency, typical quantity, and binge drinking (scored 0-12). A score of >=4 in men or >=3 in women indicates hazardous drinking / active AUD.
• CAGE Questionnaire: 4-item screen (Cut down, Annoyed by criticism, Guilty about drinking, Eye-opener). A score of >=2 is clinically positive (sensitivity 93%, specificity 76% for alcohol dependence).

Alcohol Withdrawal Syndrome: Pathophysiology & Timeline

• Pathophysiology: Chronic ethanol consumption enhances inhibitory GABA-A receptor activity and downregulates excitatory NMDA glutamate receptors. Sudden cessation or reduction of alcohol removes GABAergic inhibition and unmasks profound NMDA glutamate upregulation and central noradrenergic excess, precipitating severe neuroexcitation, autonomic storm, and delirium.

Chronological Spectrum of Alcohol Withdrawal Syndrome
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1. Mild Withdrawal (6 to 12 Hours post-cessation):
   - Autonomic: Fine postural hand tremor, tachycardia (HR >100), hypertension, diaphoresis.
   - Systemic: Anorexia, nausea, vomiting, insomnia, headache, mild anxiety.
   - Sensorium: Completely CLEAR; intact orientation to person, place, and time.

2. Alcoholic Hallucinosis (12 to 24 Hours post-cessation):
   - Perceptual Disturbances: Visual (seeing insects/animals), auditory, or tactile (formication).
   - CRITICAL BOARD PEARL: Hallucinations occur with a CLEAR SENSORIUM and INTACT ORIENTATION.
   - Vital signs are frequently normal or only mildly elevated; does NOT equal Delirium Tremens.

3. Withdrawal Seizures / "Rum Fits" (12 to 48 Hours post-cessation):
   - Seizure Type: Generalized tonic-clonic, brief, singular or in a cluster of 2 to 3.
   - Non-status; normal interictal EEG. If untreated, ~30% progress to Delirium Tremens.

4. Delirium Tremens / DTs (48 to 96 Hours [up to 7-10 days] post-cessation):
   - MEDICAL EMERGENCY: 5% to 15% mortality if untreated (circulatory collapse, arrhythmias).
   - Clinical Tetrad: Severe Delirium + Profound Global Disorientation + Visual/Tactile Hallucinations
     + Severe Autonomic Instability (malignant hypertension, HR >120, temp >38.5°C, drenching diaphoresis).
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Clinical Management Protocol & Benzodiazepine Selection

1. Objective Monitoring with CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol):
   • Quantifies 10 withdrawal parameters (nausea, tremor, sweats, anxiety, agitation, tactile/auditory/visual disturbances, headache, orientation; max score 67).
   • Score < 8: Mild withdrawal (supportive care, no pharmacotherapy needed).
   • Score 8 to 14: Moderate withdrawal (initiate symptom-triggered benzodiazepines).
   • Score >= 15: Severe withdrawal (aggressive IV benzodiazepine therapy; high risk of seizures/DTs).
2. Symptom-Triggered Benzodiazepine Protocol:
   • Administering benzodiazepines only when CIWA-Ar >=8-10 is superior to fixed-schedule dosing (results in significantly shorter treatment duration, lower total sedative dose, and reduced risk of over-sedation).
   • First-Line Agents: IV/oral Diazepam (5-10 mg) or Lorazepam (2-4 mg) titrated every 1-2 hours until patient is calm and vital signs normalize.
   • Severe Hepatic Cirrhosis, Alcoholic Hepatitis, or Geriatric Patients (LOT Mnemonic):
     • Use Lorazepam, Oxazepam, or Temazepam.
     • Pharmacologic Rationale: These agents undergo direct Phase II hepatic glucuronidation without Phase I CYP450 microsomal oxidation and generate no active metabolites. Long-acting agents (diazepam, chlordiazepoxide) undergo hepatic oxidation and produce long-lived active metabolites (nordiazepam, desmethyldiazepam) that accumulate in liver failure, precipitating hepatic encephalopathy or prolonged respiratory depression.
3. Refractory Delirium Tremens: Defined as persistent severe agitation requiring >50 mg of diazepam or >10 mg of lorazepam in the first hour. Transfer to ICU and initiate continuous IV Phenobarbital or continuous IV Propofol / Dexmedetomidine with mechanical ventilation.

Wernicke Encephalopathy & Korsakoff Syndrome

• Pathophysiology: Thiamine (Vitamin B1) deficiency leading to impaired cerebral glucose utilization, accumulation of lactate, and microvascular hemorrhages in the mamillary bodies, periventricular thalamus, and periaqueductal gray.
• Classic Clinical Triad (present in only ~30% of cases):
  1. Encephalopathy / Acute Confusion: Lethargy, profound inattention, spatial disorientation.
  2. Cerebellar Ataxia: Wide-based, staggering gait, truncal ataxia, dysmetria.
  3. Oculomotor Dysfunction: Bilateral horizontal nystagmus, bilateral lateral rectus palsy (CN VI / abducens nerve), conjugate gaze palsies.

EMERGENCY BOARD RULE: Thiamine Administration Timing High-dose IV Thiamine (500 mg IV TID for 3 to 5 days) must be administered BEFORE or SIMULTANEOUSLY WITH any intravenous dextrose or glucose-containing fluids. Mechanism: Thiamine pyrophosphate (TPP) is an indispensable cofactor for Pyruvate Dehydrogenase and Alpha-Ketoglutarate Dehydrogenase in the Krebs cycle. Administering IV glucose to a thiamine-deficient patient accelerates aerobic glycolysis, rapidly consumes all residual thiamine reserves, and triggers acute lactic acidosis, leading to permanent irreversible Korsakoff Syndrome (dense anterograde/retrograde amnesia, confabulation, apathy) or fatal brainstem herniation.