Cyanide Poisoning

Hydrogen cyanide is an extremely poisonous, colorless, flammable liquid used in multiple industries and includes rubber, plastic, and household paints. Exposure to cyanide can occur via inhalation, dermal contact, or intestinal ingestion. Cyanide poisoning is a common complication of closed-space fires since cyanide is a byproduct of plastics combustion. Symptoms develop within seconds to minutes and involve cardiovascular, respiratory, and neurological changes. Management includes sodium thiosulfate, nitrites, and hydroxocobalamin. If not recognized and treated promptly, cyanide poisoning is frequently lethal.

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Overview

Definition

Cyanide is a highly lethal mitochondrial toxin causing death within minutes to hours of exposure.

Epidemiology

  • Human exposures to cyanide 1993–2002: 3165 exposures (2.5% fatal)
  • Annual incidence in the United States: 5,000–10,000 smoke inhalation deaths
  • Industrial exposure and suicide by cyanide poisoning occur mostly in men.

Etiology

  • Domestic fires: 
    • Most common cause of cyanide poisoning
    • Byproduct of synthetic product combustion (plastic, paints)
  • Diet: ingestion of amygdalin (cyanogenic glucoside in apricot seeds)
  • Medical: 
    • Side effect of nitroprusside use (either a high dose or long-term use) 
    • Short-acting medication for hypertensive emergency results in cyanide release
  • Suicide or homicide: potassium cyanide, sodium cyanide
  • Industrial: manufacturing workplace exposure

Pathophysiology and Clinical Presentation

Pathophysiology

  • Absorbed through the skin, lungs, mucous membranes, or GI tract
  • Quickly distributed throughout the body
  • Major mechanism of action:
    • Inhibits the mitochondrial electron transport chain by the inhibition of complex IV (cytochrome c oxidase, a3 subunit) as it binds to ferric iron (Fe3+)
    • Result: blockage of oxidative phosphorylation and inhibition of aerobic ATP production
    • ATP is then produced primarily by the anaerobic pathway, resulting in lactic acid production and metabolic acidosis.
    • Result: functional histotoxic hypoxia:
      • Inability to use O2 due to poisoned electron chain
      • Especially deleterious to the cardiovascular and central nervous systems
  • Additional contributing mechanisms of cyanide:
    • Inhibition of antioxidants
    • Induction of apoptotic cell death
    • Inhibition of gamma-aminobutyric acid (GABA) formation → risk of seizures
    • Binds to hemoglobin → cyanohemoglobin (unable to transport O2)
  • Cyanide metabolism:
    • Detoxified by the rhodanese enzyme
    • Converts cyanide to water-soluble thiocyanate (needs sulfur), which is excreted in urine

Clinical presentation

Symptoms develop within seconds to minutes.

  • Breath may have a bitter or almond odor.
  • Skin:
    • Flushed or cherry red
    • Cyanosis (more common)
    • Irritant dermatitis
  • Cardiovascular:
    • Tachycardia/hypertension
    • Progression to bradycardia/hypotension
    • Dysrhythmia, cardiac arrest
  • Respiratory:
    • Tachypnea/hyperventilation (reduced PaCO2)
    • Progression to respiratory depression/failure 
    • Pulmonary edema
  • Neurologic:
    • Headache
    • Vertigo
    • Dizziness
    • Seizures
    • Coma
    • Anoxic brain injury and permanent brain damage
  • Nausea and vomiting 
  • Rhabdomyolysis
  • Renal failure
  • Hepatic necrosis
Acute cyanide poisoning

Acute cyanide poisoning:
Computed tomography scan shows diffuse cerebral edema associated with anoxic brain injury.

Image: “Brain anoxic injury” by Department of Medicine, Temple University Hospital, Philadelphia, PA 19140, USA. License: CC BY 3.0

Diagnosis and Management

Diagnosis

History and physical exam:

  • History of exposure
  • Bitter/almond smell
  • Color change of skin (flushed/cyanotic)
  • Characteristic symptoms

Laboratory tests:

  • Severe metabolic acidosis with anion gap
  • Lactic acid
  • Narrowed venous-arterial PO2 gradient (venous hyperoxia)
  • Blood cyanide level (not very reliable test)
  • Glucose (to evaluate for hypoglycemia)
  • Other tests to obtain:
    • Carboxyhemoglobin and methemoglobin: Rule out concomitant carbon monoxide (CO) exposure and ingestion of other drugs.
    • Acetaminophen and salicylate levels: Rule out coingestion of other drugs.

Management

General considerations:

  • Address any suspected cyanide poisoning quickly because of high mortality.
  • Can be hard to diagnose/recognize
  • Suspect in any smoke inhalation victim.

Decontamination:

  • Remove patient from the source.
  • Remove clothes.
  • Cleanse wounds.
  • Administer activated charcoal in the case of oral ingestion.

Resuscitation:

  • Assess airway, breathing, circulation (ABC).
  • Secure airway and provide high flow O2 (use of hyperbaric oxygenation is controversial).
  • IV fluids and pressors if needed
  • Glucose administration if hypoglycemic
  • Benzodiazepines for seizures 

Antidotes:

  • Hydroxocobalamin (vitamin B12) directly binds cyanide molecules and is the preferred treatment. 
  • Sodium thiosulfate acts as a sulfur donor for the enzyme rhodanese to convert cyanide to excretable thiocyanate.
  • Nitrites (sodium nitrite or amyl nitrite) induce methemoglobinemia:
    • Converts ferrous iron (Fe2+) to Fe3+
    • Fe3+ binds cyanide and avidly forms cyanmethemoglobin.
    • Do not use for concomitant CO poisoning as induction of methemoglobinemia can be lethal.

Differential Diagnosis

  • Methemoglobinemia: a condition of elevated methemoglobin containing oxidized Fe3+ instead of Fe2+. Methemoglobin does not bind O2. Methemoglobinemia can be caused by nitrates, dapsone, and local anesthetics and causes tissue hypoxia. Presentation includes cyanosis, headache, dizziness, nausea, seizures, shortness of breath, and/or arrhythmias. Methemoglobinemia is diagnosed with blood gas and treated with methylene blue and vitamin C administration. 
  • Carbon monoxide poisoning: an odorless, tasteless, colorless, nonirritating gas formed by hydrocarbon combustion (fires, car exhaust, gas heaters). Carbon monoxide has a higher affinity to hemoglobin than O2 and forms carboxyhemoglobin, which results in impaired O2 transport and utilization. Features include confusion, headache, dizziness, rosy cheeks, coma, and death. Diagnosis is established clinically and confirmed by blood gas. Management is 100% O2 and, if failed, hyperbaric oxygenation. 
  • Drug ingestion: various drugs can produce symptoms of poisoning similar to cyanide. The drugs include tricyclic antidepressants, salicylates, organophosphates, isoniazid, and strychnine. Detailed history and a high index of clinical suspicion are essential for correct diagnosis. Management depends on the offending agent.

References

  1. Leybell, I. (2020). Cyanide Toxicity. Emedicine. Retrieved March 24, 2021, from https://emedicine.medscape.com/article/814287-overview#a5
  2. Su, M and Desai, S. (2020). Cyanide poisoning. UpToDate. Retrieved March 24, 2021, from https://www.uptodate.com/contents/cyanide-poisoning#H2
  3. Mégarbane B, Delahaye A, Goldgran-Tolédano D, Baud FJ. (2003). Antidotal treatment of cyanide poisoning. J Chin Med Assoc. 2003;66(4):193.

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