Epidemiology

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

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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

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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

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Diagnosis

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

• Anion Gap Metabolic Acidosis (AGMA) (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]])

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

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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

• Dyspnea
• Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

Other Manifestations

• Diaphoresis/ flushing

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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

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References

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