A 48-year-old male labourer from Delhi presents to the emergency department with tremors, diaphoresis, and agitation 36 hours after his last drink. He has a 20-year history of daily alcohol consumption and has attempted withdrawal multiple times in the past. Vital signs: BP 148/92 mmHg, HR 108 bpm, temperature 37.8°C. He is oriented to person and place but not time. What is the most appropriate immediate pharmacological intervention?

Explanation

## Clinical Context This patient presents with **alcohol withdrawal syndrome** (AWS) in the acute phase, manifesting tremor, diaphoresis, agitation, autonomic hyperactivity (tachycardia, hypertension), and disorientation. The 36-hour timeline and prior withdrawal history place him at high risk for **progression to withdrawal seizures or delirium tremens**. ## Mechanism of Alcohol Withdrawal 1. Chronic alcohol use → chronic GABA~A~ receptor downregulation and glutamate upregulation 2. Abrupt cessation → loss of GABAergic inhibition 3. Unopposed glutamatergic excitation → autonomic hyperactivity, seizures, hallucinations ## Pharmacological Management **Key Point:** Benzodiazepines are the gold standard for acute alcohol withdrawal because they: - Restore GABAergic tone - Prevent seizures and progression to delirium tremens - Reduce autonomic hyperactivity **High-Yield:** In acute, severe withdrawal with autonomic instability, **IV/IM benzodiazepines (lorazepam or diazepam) are preferred over oral agents** because: - Faster onset (minutes vs. hours) - More reliable absorption in agitated patients - Allow titration to effect ("symptom-triggered" dosing) **Clinical Pearl:** Lorazepam 2–4 mg IV/IM every 5–10 minutes is the standard regimen; continue until tremor resolves, agitation subsides, or mild sedation is achieved. This is a **titration protocol**, not a fixed dose. ## Why Other Options Are Incorrect | Option | Why Wrong | |--------|----------| | Chlordiazepoxide 100 mg PO QID | Oral route is too slow for acute, severe withdrawal with autonomic instability; patient is agitated and may not tolerate PO | | Naltrexone 50 mg daily | Opioid antagonist; used for **chronic relapse prevention**, not acute withdrawal; has no role in acute AWS | | Thiamine + dextrose | Supportive measures for **prevention of Wernicke encephalopathy**; essential but NOT the primary acute intervention for withdrawal seizure risk | **Mnemonic:** **GABA DOWN** = **G**et **A**cute **B**enzodiazepines **A**s **D**ose **O**ver **W**ithdrawal **N**eeds **D**ictate ## Supportive Care - Thiamine 100 mg IV/IM (before or concurrent with dextrose to prevent Wernicke) - Correction of electrolyte abnormalities (Mg²⁺, K⁺, Ca²⁺, PO₄³⁻) - Monitoring in ICU setting given seizure risk - Fluids and nutritional support [cite:Harrison 21e Ch 474]