A 35-year-old man is admitted with cyanide poisoning following inhalation of smoke in a factory fire. He is unconscious with severe metabolic acidosis. Which agent is the drug of choice for immediate cyanide antidote therapy?

Explanation

## Management of Acute Cyanide Poisoning **Key Point:** Hydroxocobalamin is now the preferred first-line antidote for cyanide poisoning in acute settings. It directly binds cyanide to form cyanocobalamin (vitamin B₁₂), which is then excreted in urine. ### Why Hydroxocobalamin is First-Line 1. **Direct binding mechanism:** - Hydroxocobalamin has a high affinity for cyanide - Forms cyanocobalamin (non-toxic) - Rapidly excreted in urine 2. **Safety profile:** - No risk of methemoglobinemia (unlike sodium nitrite) - No hypotensive effects - Can be given in large doses without toxicity - Safe in patients with smoke inhalation (carboxyhemoglobinemia) 3. **Efficacy:** - Rapid onset (minutes) - High binding affinity for CN⁻ - Effective even in severe poisoning 4. **Dosing:** 5 g IV over 15 minutes (can repeat if needed) ### Historical Context: The Nitrite-Thiosulfate Regimen Previously, the standard was: - **Sodium nitrite** → induces methemoglobinemia (Hb-Fe³⁺) → cyanide binds to methemoglobin - **Sodium thiosulfate** → sulfurtransferase converts CN⁻ to thiocyanate (renally excreted) This regimen is now **second-line** because: - Sodium nitrite causes methemoglobinemia (dangerous in smoke inhalation with CO poisoning) - Risk of hypotension - Slower than hydroxocobalamin ### Comparison of Cyanide Antidotes | Agent | Mechanism | Onset | Safety | Current Role | |-------|-----------|-------|--------|---------------| | **Hydroxocobalamin** | Binds CN⁻ directly → cyanocobalamin | Minutes | **Excellent** — no methemoglobinemia | **First-line** | | Sodium nitrite | Induces methemoglobinemia | Minutes | **Poor** — methemoglobinemia risk, hypotension | Second-line (if hydroxocobalamin unavailable) | | Sodium thiosulfate | Converts CN⁻ to thiocyanate | Slow (hours) | Good | **Adjunctive** (with nitrite if needed) | | Dimercaprol | Heavy metal chelator | — | — | **Not indicated** — cyanide is not a metal | **High-Yield:** In acute cyanide poisoning (especially from smoke inhalation), hydroxocobalamin is preferred because it avoids the methemoglobinemia risk of nitrite in patients who may already have carboxyhemoglobinemia from CO exposure. **Clinical Pearl:** Hydroxocobalamin may turn urine and skin red (due to cyanocobalamin) — this is harmless and expected. **Mnemonic:** **CHON** = **C**yanide + **HO**xocobalamin → cyanocobalamin (excreted).