Cyanide toxicity

Background

• Sources
  • Burning of nitrogen-containing polymers (plastics, wool, silk)
  • Prolonged use of nitroprusside
• Pathophysiology
  • Binds to cytochrome oxidase in mitochondria; leads to cessation of electron transport
    • Causes switch from aerobic to anaerobic metabolism despite adequate O2

Clinical Features

Acute Intoxication

• Affected by dose, route, formulation and exposure pattern
  • Inhaled toxins more rapid than ingested
    • Inhalation exposure may cause syncope and death after only a few breaths
• Early signs
  • CNS stimulation (Headache, anxiety, confusion)
  • Tachycardia, palpitations and hypertension
  • Tachypnea
  • Cherry-red color (rarely seen)
• Late signs
  • Nausea, Vomiting
  • Bradycardia, hypotension, arrhythmias, asystole
  • Coma, Seizures (rare), Mydiriasis
  • bradypnea and pulmonary edema (non-cardiogenic), apnea
  • Renal Failure
  • Hepatic Necrosis
  • Cyanosis
  • Rhabdo, bright red venules seen on fundoscopy

Chronic

• Retrobulbar Optic Atropy (proposed)
  • Heavy smokers
• Ataxic peripheral neuropathy
• Konzo
  • Spactic upper motor neuron paraparesis seen in chronic ingestion of inadequately cooked casava

Diagnosis

1. Smell of bitter almonds (only 60-80% of population can detect this)
2. Severe unexplained metabolic acidosis (lactic)
3. PO2 of venous blood similar to arterial blood
4. normal SpO2
5. Cherry-red skin color is uncommon

Work-Up

1. Lactate
2. VBG and ABG (narrowing of the venous-arterial PO2 gradient)
3. Co-oximetry
4. Chemistry (anion gap acidosis)

Treatment

1. Supportive care
   1. O2 100% NRB
   2. IVF and vasopressors for hypotension
   3. Bicarb for acidemia (enchances of effect of nitrite and thiosulfate)
2. Antidote

Cyanokit (Hydroxocobalamin)

1. 1st line therapy
2. Mechanism of action
   1. Directly binds CN forming cyanocobalamin which is readily excreted in the urine
3. How to use:
   1. Give 70mg/kg IV over 15min (5g is standard adult dose); may repeat 5g once as needed
   2. Also give Na thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed
4. Side effects
   1. May cause temporary reddish discoloration of skin, plasma, urine, mucous membranes
      1. Interferes w/ co-oximetry measurements

Cyanide Antidote Package

1. 2nd line therapy - use if Cyanokit unavailable
2. Consider using only Na thiosulfate (no nitrites) in cases where concern for CO poisoning
3. Mechanism of action
   1. Nitrites: form metHb which binds CN more avidly than cytochrome oxidase
   2. Thiosulfate: donates its sulfur group to CN to form thiocyanate (less toxic than CN)
4. Warnings
   1. Nitrites are relatively contraindicated in pts w/ concomitant CO toxicity
      1. Induction of metHb further exacerbates O2 delivery
   2. Avoid nitrites in presence of severe hypotension if diagnosis is unclear
5. How to use:
   1. Amyl nitrite inhaled by pt (only use if unavailable to obtain IV)
      1. Hold under pt's nose for 30s of each minute, for 3 minutes
   2. Sodium nitrite 10 mg/kg IV over 5min (use instead of amyl nitrite if IV is available)
      1. Lack of measurable MetHb levels after administration confirms CN presence
      2. Monitor MetHb and keep level <30%
      3. Peds requires dosing based on Hb (see Peds dosing below)
   3. Sodium thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed

Sodium Thiosulfate (Peds Dosing)

• Max dose should not exceed 10mL
• Do not give faster than 5mL/min (to avoid hypotension)

1. Hb 7 g/dL, dose is 0.19 mL/kg of 3% sodium nitrite
2. Hb 8 g/dL, dose is 0.22 mL/kg of 3% sodium nitrite
3. Hb 9 g/dL, dose is 0.25 mL/kg of 3% sodium nitrite
4. Hb 10 g/dL, dose is 0.27 mL/kg of 3% sodium nitrite
5. Hb 11 g/dL, dose is 0.30 mL/kg of 3% sodium nitrite
6. Hb 12 g/dL, dose is 0.33 mL/kg of 3% sodium nitrite
7. Hb 13 g/dL, dose is 0.36 mL/kg of 3% sodium nitrite
8. Hb 14 g/dL, dose is 0.39 mL/kg of 3% sodium nitrite

Disposition

1. Admit all pts for obs

See Also

• Carbon Monoxide (CO)
• Hydrogen Sulfide
• Burns
• Acrylonitrile

Source

• Tintinalli
• UpToDate