A 35-year-old man is admitted to the ICU after intentional ingestion of cyanide salt. He is unconscious, with a blood pressure of 70/40 mmHg, heart rate 140/min, and respiratory rate 28/min. Arterial blood gas shows severe metabolic acidosis (pH 6.9, lactate 15 mmol/L). Which of the following is the most appropriate immediate antidote?

Explanation

## Cyanide Poisoning: Acute Management **Key Point:** Hydroxocobalamin (5 g IV) is the **preferred first-line antidote** for acute severe cyanide poisoning, particularly in hemodynamically unstable patients, as it directly binds cyanide without inducing methemoglobinemia or worsening hypotension. ### Pathophysiology of Cyanide Toxicity 1. Cyanide (CN⁻) binds to Fe³⁺ in cytochrome c oxidase in the inner mitochondrial membrane 2. Blocks electron transport chain → anaerobic metabolism → severe lactic acidosis 3. Causes "histotoxic hypoxia" (tissues cannot use oxygen despite normal PaO₂) 4. Rapid onset: loss of consciousness, seizures, cardiac arrhythmias, death within minutes ### Why Hydroxocobalamin is the Correct Answer This patient presents with: - **Hemodynamic collapse** (BP 70/40 mmHg) — cardiogenic/distributive shock from cyanide - **Severe metabolic acidosis** (pH 6.9, lactate 15 mmol/L) — profound cellular hypoxia - **Unconsciousness** — CNS involvement **Sodium nitrite (Option B)** is contraindicated or relatively contraindicated in this scenario because: - It induces **methemoglobinemia**, which reduces the oxygen-carrying capacity of blood — catastrophic in a patient already in shock - It causes **vasodilation and hypotension**, which would further worsen BP of 70/40 mmHg - In a patient with hemodynamic collapse, adding methemoglobinemia can precipitate cardiac arrest **Hydroxocobalamin (Option C)** is the correct choice because: - **Mechanism:** Vitamin B₁₂ analogue; the cobalt ion directly binds CN⁻ to form cyanocobalamin, which is renally excreted - **Dose:** 5 g IV over 15 minutes (may repeat once or twice in severe cases) - **Onset:** Rapid — begins binding cyanide within minutes of administration - **Hemodynamic safety:** Does NOT cause methemoglobinemia; does NOT lower blood pressure; may actually have mild vasopressor properties - **CNS penetration:** Superior to nitrite-based regimens - **Preferred in:** Acute severe poisoning, especially with hemodynamic instability, smoke inhalation (where co-existing CO poisoning makes methemoglobin induction dangerous) ### Antidote Comparison | Feature | Sodium Nitrite + Thiosulfate | Hydroxocobalamin | |---------|------------------------------|------------------| | **Mechanism** | MetHb binding + enzymatic conversion | Direct CN⁻ chelation | | **Effect on BP** | ↓↓ (vasodilation) | Neutral / mild ↑ | | **Methemoglobinemia** | Yes (toxic risk) | No | | **Preferred in** | Stable patients, resource-limited settings | Hemodynamically unstable, smoke inhalation | | **Current guideline** | Traditional (older) | First-line (modern guidelines) | | **Cost** | Low | Higher | ### Why Other Options Are Wrong - **Option A (Thiosulfate first, then nitrite):** Incorrect sequence even in the traditional regimen; nitrite must precede thiosulfate. Also, nitrite is contraindicated here. - **Option B (Nitrite then thiosulfate):** Traditional regimen but dangerous in this hypotensive patient — nitrite-induced methemoglobinemia and vasodilation would worsen shock. - **Option D (Ethanol IV):** Ethanol has no role in cyanide poisoning. It is used as an antidote for methanol and ethylene glycol poisoning (competitive inhibition of alcohol dehydrogenase). This is a distractor. **Clinical Pearl:** Per current toxicology guidelines (Goldfrank's Toxicologic Emergencies, 11e; Harrison's 21e Ch 471), **hydroxocobalamin is the first-line antidote** for cyanide poisoning, especially in critically ill or hemodynamically unstable patients. The traditional nitrite-thiosulfate kit is reserved for settings where hydroxocobalamin is unavailable. [cite: Goldfrank's Toxicologic Emergencies 11e; Harrison 21e Ch 471; KD Tripathi 8e Ch 12]