Cyanide

Epidemiology

  • Lethal dose of potassium or sodium cyanide: 200-300 mg
  • Lethal dose of hydrocyanic acid: 50 mg

Exposures

Fire/Smoke Inhalation (see Smoke Inhalation, [[Smoke Inhalation]])

  • Epidemiology
    • Fire/Smoke Inhalation is the Most Common Etiology of Cyanide Intoxication in Industrialized Countries
    • Significant Levels of Cyanide are Present in Approximately 33% of All Fire Victims
  • Chemistry: cyanide may be liberated during the combustion of materials containing both carbon and nitrogen
    • Combustion of Melamine Resins: found in household items
    • Combustion of Polyacrylonitriles: found in plastics
    • Combustion of Polyurethane: found in insulation and upholstery
    • Combustion of Silk
    • Combustion of Synthetic Rubber
    • Combustion of Wool

Industrial Exposure

Routes of Absorption

  • Dermal Exposure: due to splashes from cyanide solutions, etc
    • Cyanide May Be Absorbed Through the Skin and is Rapidly Absorbed Across Mucous Membranes
  • Inhalation
    • Cyanide is Rapidly Absorbed Across Mucous Membranes
  • Ingestion
    • Cyanide is Rapidly Absorbed Across Mucous Membranes

Sources

  • Cyanide Salts: skin contact may result in burns (which increases skin absorption of cyanide
    • Electroplating in Jewelry Manufacturing: combination of cyanide salts and acid may result in the release of cyanide gas (which can result in lethal inhalational exposures)
    • Hair Removal from Hides
    • Metal Cleaning
    • Metallurgy
    • Ore Refining
    • Photography
  • Nitriles (Organic Cyanide Compounds)
    • Artificial Nail Polish Removers: contains acetonitrile
    • Fumigant Rodenticides
    • Synthetic Plastic and Rubber Manufacturing

Medical Administration

Sources

  • Amygdalin (Laetrile) (see Amygdalin, [[Amygdalin]])
    • Epidemiology: used as an anti-neoplastic medication during the 1950’s
    • Pharmacology derived from apricot and peach seeds
      • Intestinal β-D-glucosidase metabolizes amygdalin, releasing hydrogen cyanide: this reaction explains why only gastrointestinal administration (as opposed to intravenous administration) results in toxicity
  • Nitroprusside (Nipride) (see Nitroprusside, [[Nitroprusside]])
    • Risk Factors for Toxicity
      • Acute Kidney Injury (AKI)/Chronic Kidney Disease (CKD) (see Acute Kidney Injury, [[Acute Kidney Injury]] and Chronic Kidney Disease, [[Chronic Kidney Disease]])
      • Prolonged Infusion
      • Use in Pediatric Patients
    • Pharmacology: nitroprusside contains five cyanide groups per molecule
    • Clinical
      • Fatalities May Occur with Infusions of 5-10 μg/kg/min x 3-10 hrs
    • Prevention of Toxicity
      • Addition of Sodium Thiosulfate to Nitroprusside Solution
      • Maximal Infusion Rate of 2 μg/kg/min
      • Use of Silver Foil on Intravenous Tubing: prevents light from decomposing nitroprusside molecule

Dietary Ingestion

Sources

  • Cyanogenic Glycosides from Rosaceae Family Fruit/Nuts: these contain cyanogenic glycosides (such as amygdalin) in their seeds/pits
    • Apple Seeds
    • Apricot Seeds
    • Bean Seeds
    • Bitter Almond: note that the common “sweet” almond does not cause cyanide intoxication
    • Cherry Seeds
    • Chokeberry Seeds
    • Crabapple Seeds
    • Peach Seeds
    • Pear Seeds
    • Plum Seeds
  • Other Food Which Contain Possible Cyanogens
    • Bamboo Shoots
    • Cassava Root
    • Soy

Other

Sources

  • During Illicit Synthesis of Phencyclidine (see Phencyclidine, [[Phencyclidine]])
  • Terrorist Attack
  • Tobacco Abuse (see Tobacco, [[Tobacco]])
    • Epidemiology: smokers have approximately 2.5x higher blood cyanide levels than non-smokers
    • Physiology: natural cyanide is found in tobacco

Physiology

  • Inhibition of mitochondrial ferricytochrome oxidase and blocking of electron transport (with subsequent decreased oxidative phosphorylation and oxygen utilization) -> uncoupled oxidative phosphorylation -> lactic acidosis
  • Rapid absorption from stomach (reacts with hydrochloric acid to form hydrocyanic acid, which is absorbed as cyanide ion), lungs, mucous membranes, and unbroken skin
  • 60% protein bound
  • Concentrated in RBC
  • Volume of distribution: 1.5 L/kg of BW
  • Mitochondrial Metabolism: by rhodanase enzyme, which mediates transfer of sulfur from thiosulfate to cyanide ion, forming relatively non-toxic thiocyanate (which is excreted renally)

Nitroprusside Intoxication

  • Thiocyanate toxicity -> uncoupling of oxidative phosphorlyation -> lactic acidosis

Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

Serum Lactate (see Serum Lactate, [[Serum Lactate]])

  • Elevated

Serum Cyanide Level (see Serum Cyanide, [[Serum Cyanide]])

  • Roughly correlates with clinical manifestations
    • <8 µmol/L (<0.02 mg/L): no symptoms
    • 20-40 µmol/L (0.05-0.1 mg/L): flushing/ tachycardia
    • 40-100 µmol/L (0.1-0.25 mg/L): obtundation
    • 100-200 µmol/L (0.25-0.3 mg/L): coma/ respiratory depression
    • >120 µmol/L (>0.3 mg/L): may be fatal

Swan-Ganz (Pulmonary Artery) Catheterization (see Swan-Ganz Catheter, [[Swan-Ganz Catheter]])

  • Narrowed A-V O2 difference: due to impaired tissue extraction of oxygen

Clinical Manifestations

General Comments

  • Onset: effects begin within seconds of inhalation or within 30 min of ingestion

Cardiovascular Manifestations

  • Tachycardia and Hypertension (see xxxx, [[xxxx]]): early
  • Bradycardia and Hypotension (see xxxx, [[xxxx]])): later
  • Tachy or Bradyarrhythmias
  • Nodal or Idioventricular Rhythms
  • Third degree heart block

Gastrointestinal Manifestations

Bitter Almond Odor on Breath

  • xxxx

Burning Sensation in Mouth and Throat

  • xxx

Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])

  • xxxx

Neurologic Manifestations

  • Headache
  • Faintness
  • Vertigo
  • Agitation
  • Anxiety
  • Coma
  • Seizures
  • Opisthotonus
  • Trismus
  • Paralysis
  • Respiratory depression

Pulmonary Manifestations

Other Manifestations

  • Diaphoresis/ flushing

Treatment

Lilly Cyanide Antidote Kit

(may need to treat before levels are available)

  • Nitrites induce methemoglobinemia -> MetHb has high affinity for cyanide -> thiosulfate reacts with cyanide that is released from cyano-MetHb -> forms thiocyanate (which is then excreted renally)
  • Amyl Nitrite: inhalation for 30 sec of each min (new ampule q3 min)
    • May be omitted if sodium nitrite is available
  • Sodium Nitrite: 3% solution IV at 2.5-5.0 mL/min to total of 10-15 mL (300-450 mg)
    • Use 10 mg/kg in children
    • May repeat half or full dose for recurrent symptoms
  • Sodium Thiosulfate: 25% solution, give 50 mL IV over 1-2 min
    • Use 0.5 g/kg in children
    • May repeat half or full dose for recurrent symptoms

GI Decontamination

  • Ipecac: contraindicated (due to rapid onset of cyanide toxicity)
  • Charcoal: poorly absorbs cyanide
  • NG tube:

Oxygen (100%)

  • Reverses binding of cyanide to cytochrome oxidase and enhances efficacy of Sodium Thiosulfate and Nitrites
  • Replenishes oxygen in mitochondria needed for metabolism

Hyperbaric Oxygen

  • Not proven to be of any benefit

Cyanocobolamin

  • Not effective

Methylene Blue

  • Although not used currently, large doses of methylene blue can be used to treat potassium cyanide poisoning (method first tested in 1933 by Dr. Matilda Moldenhauer Brooks, San Francisco)
    • The reduction potential of methylene blue is similar to oxygen and can be reduced by the electron transport chain

References

  • Matilda Moldenhauer Brooks (1936). “Methylene blue as an antidote for cyanide and carbon monoxide poisoning”. The Scientific Monthly 43 (6): 585–586