Cyanide

Aka: Cyanide, Hydrogen cyanide, Hydrocyanic acid, Cyanogen chloride

1. See Also
   1. Chemical Weapon
2. Mechanism
   1. Site of action
      1. Inhibits Cytochrome A3
      2. Absorbed effect (Hydrogen cyanide, Cyanogen chloride)
         1. Binds ferric ions in mitochondrial cytochromes
         2. Cell unable to perform aerobic metabolism
      3. Local respiratory effects (Cyanogen chloride)
         1. Pulmonary Intoxicant (Chlorine type effect)
   2. State
      1. Temperature below 78 F: Liquid and Vapor
      2. Temperature above 78 F: Gas
   3. Route of exposure
      1. Percutaneous
      2. Inhalation
         1. Life threatening dose: 110 ppm for 30 min
         2. Lethal dose: 270 ppm
      3. Ingestion
         1. Lethal dose: >200 mg
3. Sources
   1. Weapon or intentional toxin
   2. Tobacco Smoking (0.4 mcg/ml)
   3. Foods: Fruits, seeds and pits
      1. Prunus Seeds (plums, cherries, peaches, nectarines, apricots and almonds)
      2. Lima beans
      3. Cassava plant roots (staple in some parts of world)
   4. Smoke Inhalation (Structure fires)
      1. Especially plastics (acrylonitrile)
   5. Industrial use Hydrogen cyanide (300,000 tons)
   6. Nitroprusside metabolite
4. Agents
   1. Hydrogen cyanide (Hydrocyanic acid, AC)
   2. Cyanogen chloride (CK)
5. Symptoms: Low level Cyanide Vapor exposure
   1. Intense eye, nose and airway irritation
   2. Increased Rate and depth of breathing
   3. Dizziness
   4. Headache
   5. Agitation
   6. Confusion
   7. Nausea, Vomiting and Abdominal Pain (with ingestion)
6. Signs: High Cyanide Vapor exposure
   1. Immediate
      1. Diaphoretic
      2. Pupils normal or large
      3. Hypertension and reflex Tachycardia
   2. Effects at time 15 Seconds
      1. Transient increased Breathing Rate, depth
   3. Effects at time 30 Seconds:
      1. Seizure
   4. Effects at time 2 to 4 Minutes
      1. Respiratory arrest from central apnea
   5. Effects at time: 4 to 8 Minutes
      1. Terminal Hypotension
      2. Bradyarrhythmia
      3. Cardiac Arrest
   6. Effects at time 6 to 8 Minutes
      1. Death
7. Signs: Presentations
   1. Acidemia or acute confusion AND
      1. Syncope in lab or industrial worker
      2. Smoke Inhalation
      3. Suicide attempt
      4. Ingestion (e.g. Prunus seed, Acetonitrile)
8. Labs
   1. Whole Blood Serum Cyanide effects
      1. Results are typically delayed
      2. Mild effects: 0.5-1.0 mcg/ml
      3. Lethal effects: >2.5 to 3 mcg/ml
   2. Arterial Blood Gas
      1. Metabolic Acidosis with High Anion Gap
      2. Serum Lactic Acid high
   3. Lactic Acid
      1. Typically elevated >8 mmol/L
9. Differential Diagnosis
   1. Nerve Agent
      1. Miosis
      2. Increased Rhinorrhea and oral secretions
   2. Hydrogen Sulfide
      1. Rotten egg odor
   3. Carbon Monoxide Poisoning
      1. Pink, healthy looking skin with Hypoxia
10. Detection
    1. Odor
       1. Bitter almonds (Only detectable by 50% of people)
    2. Detection Kits
       1. Hydrogen cyanide (AC)
          1. M256A1 (7.0 mg/m3)
          2. M272 (20.0 mg/m3)
          3. ICAD (250 mg/m3)
          4. M18A2 (8.0 mg/m3)
          5. M90 (30 mg/m3)
       2. Cyanogen chloride (CK)
          1. MINICAMS (130 ppbv)
          2. Draeger (0.25-5 ppm)
          3. M93A1 Fox (46 mg/m3)
11. Management: General
    1. Decontamination
       1. Vapor: None (other than removal from exposure)
          1. Minimal risk of off-gassing
       2. Liquid: Remove clothes, brush off dry powders and wash skin with soap and water
       3. Ingestion
          1. May consider Activated Charcoal if acute ingestion and controlled airway
    2. Supportive care
       1. Oxygen at 100% via Non-Rebreather Mask
       2. Stabilize airway
       3. Correct acidosis
       4. Intravenous FluidResuscitation if hypotensive
    3. Disposition
       1. Other patients, with normal serum bicarbonate and Lactic Acid: Observe for 4 to 6 hours
       2. Observe ingestion patients for longer period
12. Management: Antidotes
    1. Antidote: Cyanokit (IV Hydroxycobalamin)
       1. Indications: Smoke Inhalation (Paris Fire Brigade Protocol)
          1. Known Smoke Inhalation in an enclosed space AND
          2. One of the following criteria
             1. Altered Mental Status
             2. Soot in nares or mouth
             3. Full cardiopulmonary arrest (without full body burns incompatible with life)
       2. Dosing
          1. Adult: Hydroxycobalamin (Vitamin B12a) 5 grams IV over 15 minutes
          2. Child: Hydroxycobalamin (Vitamin B12a) 70 mg/kg (up to 5 g) IV over 15 minutes
       3. Efficacy
          1. Resulted in 50% ROSC rate in full arrest Smoke Inhalation patients
          2. Much safer empiric therapy than the Lily Kit (Methemoglobinemia, Hypotension)
       4. References
          1. Fortin (2006) Clin Toxicol 44 (suppl 1):37-44 +PMID:16990192 [PubMed]
          2. Borron (2007) Ann Emerg Med 49(6): 794-801 +PMID:17481777 [PubMed]
    2. Antidote: Lily Kit (2 Step Process)
       1. First: Sodium Nitrite to form Methemoglobin
          1. Dosing: Sodium Nitrite
             1. Adult: 300 mg (10 ml) IV (1 ampule of Pasadena kit) at 2.5 to 3 ml/min
             2. Child: 0.33 ml/kg of 3% solution IV over 10 min
          2. Alternative
             1. Amyl Nitrate crushed and inhaled
          3. Contraindications
             1. Concurrent Carbon Monoxide Poisoning (e.g. Smoke Inhalation)
                1. Further interferes with Hemoglobin oxygen carrying capacity
          4. Adverse effects
             1. Hypotension (Nitrites related)
             2. Methemoglobinemia with secondary Hypoxemia
          5. Mechanism
             1. Convert Hemoglobin iron from ferrous (Fe 2+) to ferric (Fe 3+)
             2. Cyanide selectively binds methemoglobin instead of mitochondria
       2. Next: Sodium thiosulfate to act as sulfur donor
          1. Adult: 12.5 g or 50 ml (1 large bottle in Pasadena kit, 25% solution)
          2. Child: 250 mg/kg or 1.65 ml/kg (up to 12.5 g) IV of 25% standard solution
          3. Allows for enzymatic conversion (via rhodanese) of Cyanide to a renally excreted form
13. Prevention
    1. Activated Charcoal in chemical protective mask
       1. Absorbs Cyanide and provides full protection
14. Triage
    1. Immediate
       1. Presentation within minutes of exposure
       2. Seizures or recent apnea with circulation intact
    2. Minimal
       1. Mild effects and out of exposure
    3. Delayed
       1. Recovering from mild effects or successful therapy
    4. Expectant
       1. Apnea and circulatory failure
    5. Course
       1. Observe survivors for 24-48 hours after exposure
15. References
    1. Koch (2016) Crit Dec Emerg Med 30(9): 23
    2. Mell in Herbert (2015) EM:RAP 15(3): 4-5
    3. Medical Response to Chemical Warfare and Terrorism
       1. US Army Medical Research Institute Chemical Defense
       2. Video-Teleconference: 4/20/00 to 4/22/99
       3. Video-Teleconference: 12/5/00 to 12/7/00
       4. Text: 3rd Edition, December 1998