A 28-year-old woman is admitted to the ICU with suspected cyanide poisoning from ingestion of cassava root (containing cyanogenic glycosides). She is drowsy, has a respiratory rate of 32/min, and blood pressure is 88/54 mmHg. Arterial blood gas shows severe metabolic acidosis (pH 7.15, HCO₃⁻ 10 mEq/L) and lactate 10.5 mmol/L. She has already received sodium nitrite 10 mL IV and sodium thiosulfate 50 mL IV 15 minutes ago but remains critically ill. What is the most appropriate next step?

Explanation

## Clinical Scenario Analysis This patient has: - **Ingestion** of cyanide (cassava root—slower absorption than inhalation) - **Persistent severe symptoms** despite initial antidote therapy (nitrite + thiosulfate 15 min ago) - **Worsening metabolic acidosis** (pH 7.15, lactate 10.5 mmol/L) - **Hypotension** (88/54 mmHg)—sign of cardiovascular collapse The initial two-agent regimen has failed to reverse poisoning, indicating either inadequate dosing, continued cyanide absorption, or need for a more potent antidote. ## Antidote Hierarchy for Refractory Cyanide Poisoning ```mermaid flowchart TD A[Cyanide poisoning diagnosed]:::outcome --> B[Initial therapy: Nitrite + Thiosulfate]:::action B --> C{Response in 5-10 min?}:::decision C -->|Good| D[Continue supportive care]:::action C -->|Poor/Refractory| E[Reassess: continued absorption?]:::decision E -->|Ingestion with poor response| F[Add Hydroxocobalamin 5g IV]:::action E -->|Inhalation with poor response| G[Repeat nitrite/thiosulfate]:::action F --> H[Hydroxocobalamin binds CN⁻ directly]:::outcome H --> I[Forms cyanocobalamin excreted in urine]:::outcome I --> J[More effective than nitrite for ingestion]:::outcome ``` ## Comparison of Antidotes | Antidote | Mechanism | Onset | Best Use | Advantage | |----------|-----------|-------|----------|----------| | **Sodium Nitrite** | Induces MetHb; CN⁻ binds MetHb | 2–3 min | Inhalation/IV cyanide | Rapid | | **Sodium Thiosulfate** | Enzymatic conversion CN⁻ → thiocyanate | 15–30 min | All routes | Safe, repeatable | | **Hydroxocobalamin** | Direct binding CN⁻ → cyanocobalamin | 5–10 min | Ingestion, refractory cases | No methemoglobinemia risk | **High-Yield:** Hydroxocobalamin is increasingly preferred over sodium nitrite, especially for: - Ingested cyanide (slower absorption allows time for direct binding) - Refractory cases (when nitrite + thiosulfate fail) - Patients with methemoglobinemia risk (anemia, cardiac disease, G6PD deficiency) ## Why Hydroxocobalamin in This Case **Key Point:** This patient has ingested cyanide (cassava root) with **persistent severe acidosis and hypotension** 15 minutes after initial therapy. Hydroxocobalamin directly binds free cyanide in plasma and tissues, forming cyanocobalamin, which is excreted renally. It is more effective than repeated thiosulfate for ingestion and does not carry the risk of methemoglobinemia. **Clinical Pearl:** Hydroxocobalamin is now the **preferred antidote in many toxicology centers** (especially Europe and increasingly in the US) because it: - Works faster than thiosulfate - Does not induce methemoglobinemia - Can be given in higher doses without toxicity - Is effective for all routes of cyanide exposure ## Dosing and Administration - **Hydroxocobalamin:** 5 g IV over 15 minutes (can repeat once if needed) - Follow with sodium thiosulfate 50 mL IV to handle any residual cyanide - Urine may turn red (due to cyanocobalamin excretion)—benign ## Supportive Measures for Hypotension - IV fluids (cautiously—risk of pulmonary edema) - Vasopressors (norepinephrine) if hypotensive despite fluids - Sodium bicarbonate for severe acidosis (pH < 7.1) - Mechanical ventilation if respiratory depression worsens **Mnemonic:** **HYDROXY-COBAL** = Hydroxocobalamin for **refractory** cyanide (ingestion, persistent symptoms). [cite:Park 26e Ch 12; Poisoning & Toxicology; Micromedex Cyanide Poisoning Guidelines]