A 35-year-old woman is brought to the emergency department in coma after accidental inhalation of hydrogen cyanide gas in an industrial accident. She is profoundly hypotensive (BP 70/40), has a respiratory rate of 8/min, and fixed dilated pupils. Immediate blood cyanide level is pending. Which of the following is the most appropriate immediate antidote to administer?

Explanation

## Immediate Management of Acute Cyanide Poisoning **Key Point:** Hydroxocobalamin is the first-line antidote for cyanide poisoning in modern toxicology because it directly binds cyanide with high affinity and has an excellent safety profile. ### Antidote Comparison | Antidote | Mechanism | Advantages | Disadvantages | Current Role | |----------|-----------|-----------|---------------|---------------| | **Hydroxocobalamin** | Binds CN⁻ → cyanocobalamin (excreted in urine) | High affinity, rapid onset, no hypotension, safe in pregnancy | Expensive, may turn urine red | **First-line** | | **Sodium nitrite** | Induces methemoglobinemia (competes for CN⁻) | Rapid, inexpensive | Causes hypotension, methemoglobinemia toxic, contraindicated in smoke inhalation (CO present) | Adjunct only (rarely used now) | | **Sodium thiosulfate** | Provides sulfur for rhodanese enzyme to convert CN⁻ → thiocyanate | Slow onset, safe | Requires 24–48 hrs for full effect, weak alone | Used with hydroxocobalamin if available | | **Methylene blue** | Oxidizes CN⁻ to cyanate | — | No proven efficacy in cyanide poisoning | **Not indicated** | | **N-acetylcysteine** | Antioxidant, no direct CN⁻ binding | — | No role in cyanide toxicity | **Not indicated** | **High-Yield:** Hydroxocobalamin is preferred because: 1. **Direct binding**: Irreversibly binds CN⁻ with Kd ~10⁻¹⁴ (extremely high affinity) 2. **No hypotension**: Unlike sodium nitrite, does not induce vasodilation 3. **Safe in all scenarios**: Effective in smoke inhalation (where CO is also present) 4. **Pregnancy-safe**: No teratogenic risk ### Why Sodium Nitrite is Suboptimal Here **Warning:** Sodium nitrite is **contraindicated or should be avoided** in this patient because: - She is already **severely hypotensive** (BP 70/40); nitrite will worsen hypotension - In industrial cyanide exposure, **carbon monoxide may also be present** (e.g., from incomplete combustion); sodium nitrite worsens CO poisoning by inducing methemoglobinemia - Modern guidelines favor hydroxocobalamin monotherapy over the older nitrite-thiosulfate cyanide antidote kit ### Treatment Algorithm ```mermaid flowchart TD A[Suspected acute cyanide poisoning]:::outcome --> B[Remove from source, 100% O₂]:::action B --> C{Hypotensive?}:::decision C -->|Yes| D[Hydroxocobalamin 70 mg/kg IV]:::action C -->|No| E{Smoke inhalation?}:::decision E -->|Yes| D E -->|No| F[Hydroxocobalamin OR nitrite-thiosulfate kit]:::action D --> G[Supportive care: fluids, vasopressors]:::action F --> G G --> H[Monitor cyanide level, lactate]:::action H --> I[Repeat hydroxocobalamin if needed]:::action ``` **Clinical Pearl:** In this patient with profound hypotension and respiratory depression, hydroxocobalamin is the safest choice. If hydroxocobalamin is unavailable and cyanide poisoning is certain, **sodium thiosulfate alone** (without nitrite) is preferred over the full antidote kit to avoid worsening hypotension. ### Dosing & Administration - **Hydroxocobalamin**: 70 mg/kg IV bolus (typically 5 g for adults) over 15 minutes - Can repeat once if clinical deterioration or cyanide level remains elevated - **Sodium thiosulfate** (if used): 12.5 g IV bolus (may be given after hydroxocobalamin for synergy) **Mnemonic:** **HYDROXO** = **H**igh affinity, **Y**ield rapid effect, **D**irect binding, **R**eliable, **O**ptimal first-line