Cyanide Poisoning

Cyanide poisoning blocks cellular respiration. Cyanide binds the ferric ion of cytochrome c oxidase (complex IV) in mitochondria, stopping aerobic ATP production, so cells shift to anaerobic metabolism and lactic acidosis follows. Tissues with high oxygen demand (brain, heart) fail first. Venous blood stays oxygenated because tissues cannot use oxygen, so the skin may look pink.

Sources

• Smoke inhalation in enclosed-space fires (burning plastics, wool and polyurethane release hydrogen cyanide)
• Industrial exposure (electroplating, mining, jewelry, chemical synthesis, photography)
• Ingestion of cyanide salts (potassium cyanide, deliberate)
• Sodium nitroprusside infusion (especially high rate or prolonged)
• Plant glycosides: cassava (linamarin), bitter almond and apricot kernels (amygdalin)
• Acetonitrile and nail polish remover in children

Oral lethal dose of potassium cyanide is about 200 mg (1 to 3 mg/kg). Inhalation of hydrogen cyanide above 270 parts per million is fatal within minutes. Chronic dietary exposure to inadequately processed cassava causes konzo, a spastic paraparesis, and tropical ataxic neuropathy. Complications: cardiac arrest, seizures, anoxic brain injury and delayed parkinsonism.

• Rapid onset after inhalation: headache, dizziness, anxiety, dyspnea, nausea, tachypnea
• Then confusion, seizures, coma, hypotension, bradycardia, arrhythmia and respiratory arrest
• Bitter almond odor (not detected by many people)
• Bright red venous blood, with cyanosis late
• Severe lactic acidosis with a high anion gap
• Fire victims: soot in the mouth or nose, carbonaceous sputum, singed hair, and carbon monoxide co-poisoning
• Red flags: coma, seizures, hypotension, lactate over 8 mmol/L and a history of enclosed-space fire exposure

1. Clinical diagnosis, and treat on suspicion. Do not delay antidote for laboratory results.
2. Plasma lactate: over 8 mmol/L in a smoke inhalation victim has high specificity for cyanide, and over 10 mmol/L supports severe poisoning.
3. Arterial and venous blood gas: narrowed arteriovenous oxygen difference, metabolic acidosis, and a raised anion gap.
4. Co-oximetry for carboxyhemoglobin and methemoglobin (the venous oxygen saturation is abnormally high).
5. Whole blood cyanide level (over 0.5 mg/L is toxic, over 2.5 to 3.0 mg/L is fatal) is slow and does not guide treatment.
6. ECG, glucose, electrolytes, creatinine, chest radiograph.

Differentials: carbon monoxide poisoning, hydrogen sulfide poisoning, methemoglobinemia, other causes of lactic acidosis, sepsis, organophosphate poisoning.

1. Remove from the source: rescuers must use protection (self-contained breathing apparatus). Remove and bag contaminated clothing and wash skin with soap and water.
2. Oxygen: 100% by high-flow mask or intubate and ventilate.
3. Hydroxocobalamin (first-line antidote): 5 g IV over 15 minutes (children 70 mg/kg, maximum 5 g). A second 5 g dose over 15 minutes to 2 hours for persistent instability, and up to 10 g in total. Adverse effects: red discoloration of skin, plasma and urine for days, interference with co-oximetry and colorimetric tests (draw blood before dosing), transient hypertension, and rash. Give through a separate line from blood products and other drugs.
4. Sodium thiosulfate: 12.5 g (50 mL of 25% solution) IV over 10 minutes (children 250 mg/kg, maximum 12.5 g), as an adjunct to hydroxocobalamin in severe poisoning (it acts more slowly). Give through a separate line.
5. Sodium nitrite only when hydroxocobalamin is unavailable and carbon monoxide co-poisoning is excluded: 300 mg (10 mL of 3%) IV over 5 minutes (children 4.5 to 10 mg/kg, maximum 300 mg), followed by sodium thiosulfate. It causes hypotension and methemoglobinemia, so avoid in smoke inhalation.
6. Supportive care: IV crystalloid and norepinephrine 0.05 to 0.5 micrograms/kg/min for hypotension, sodium bicarbonate 1 to 2 mmol/kg IV for pH under 7.1, lorazepam 4 mg IV for seizures (children 0.1 mg/kg), and cardiopulmonary resuscitation when arrested.
7. Oral ingestion: activated charcoal 50 g orally within 1 hour once the antidote is given and the airway secured.
8. Nitroprusside-related cyanide toxicity: stop the infusion, and give hydroxocobalamin 5 g IV. Co-infuse sodium thiosulfate (a ratio of 10 mg of thiosulfate to 1 mg of nitroprusside) in prolonged use.

Prevention: cassava should be soaked, dried or fermented thoroughly before eating. Industrial exposure needs ventilation and monitoring, with antidote kits available at the workplace. Follow-up includes neurologic review after severe exposure.