Cyanide

Factsheet
Cyanide
Updated November 2, 2022
Background
Cyanide is a naturally occurring chemical, found in many plants, that has been used in
conventional warfare and poisoning for more than two millennia.1 It is highly lethal, whether
inhaled as a gas, ingested in solid form, or absorbed through topical exposure. Two notable
incidents in recent history include the Jonestown Massacre in 1978 and the Tylenol poisonings in
1982, which highlight the lethality of this poison. Despite its historical use as a chemical warfare
agent, the most common cause of cyanide poisoning is smoke inhalation from fires.
First isolated in 1782, cyanide is a compound composed of carbon atom triple-bonded to a

nitrogen atom (C≡N). Cyanide is a naturally occurring chemical can be produced by certain types
of bacteria, fungi, and algae and found in several types of plants, seeds, and fruit stones, including
bamboo, cassava, bitter almonds, apples, and peaches. Despite its toxicity, cyanide has many
roles in industry and medicine. In industry, it is used in manufacturing, pesticides, and can be
found in several industrial chemicals.2,3 In medicine, cyanide can be found in the widely used
antihypertensive sodium nitroprusside, each molecule of which contains 5 ions of cyanide.
Use as Chemical Warfare Agent

Because it is a fast-acting and highly lethal chemical, cyanide poses an ongoing threat as a weapon
of terrorism, whether it is delivered in oral form via sodium cyanide and potassium cyanide or as a
gas via hydrogen cyanide and cyanogen chloride.
The use of cyanide in warfare dates to Roman Emperor Nero (37–68 CE), who used cyanide-
containing cherry laurel water as a poison. Cyanide was also used during the Franco-Prussian War
(1870–1871), during which Napoleon III urged his troops to dip their bayonet tips in the poison.
Both World Wars saw the use of cyanide: during World War I, it was employed by French and
Austrian troops; during World War II, Nazi Germany used the rodenticidal product Zyklon B to kill
millions of people. In the 1980s, cyanide may have been used in the Iran-Iraq War, on the Kurds in
Iraq, and in Syria. In 1995, the Japanese cult Aum Shinrikyo placed cyanide in subway bathrooms.
Mechanism of Action and Toxicokinetics

Cyanide poisons the mitochondrial electron transport chain within cells and renders the body
unable to derive energy (adenosine triphosphate—ATP) from oxygen.4 Specifically, it binds to the
a3 portion (complex IV) of cytochrome oxidase and prevents cells from using oxygen, causing rapid
death.
Airborne release of cyanide gas, in the form of hydrogen cyanide or cyanogen chloride, would be
expected to be lethal to 50% of those exposed (LCt50) at levels of 2,500–5,000 mg•min/m^3 and
11,000 mg•min/m^3, respectively. When ingested as sodium or potassium cyanide, the lethal dose
is 100–200 mg.
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Factsheet
Cyanide
Signs and Symptoms

Cyanide kills quickly; death occurs within seconds of a lethal dose of cyanide gas and within
minutes of ingestion of a lethal dose of cyanide salt.2 The central nervous system (CNS) and
cardiovascular systems are chiefly affected. Signs and symptoms of cyanide poisoning include the
following:
• CNS: headache, anxiety, agitation, confusion, lethargy, seizures, and coma
• Cardiovascular: decreased inotropy, bradycardia followed by reflex tachycardia,
hypotension, and pulmonary edema
• Other: acute lung injury, nausea and vomiting, cherry-red skin color.
Survivors may suffer Parkinson’s disease, ataxia, optic atrophy, and other neurologic disorders.
Diagnosis
Cyanide intoxication is largely a clinical diagnosis; however, several laboratory features are
suggestive:
• Metabolic acidosis (increased anion gap)
• Elevated lactic acid
• Venous oxygen saturation > 90%.
Cyanide blood levels are confirmatory, as results are not obtainable in time for initial diagnosis.1
There are some reports of use of rapid calorimetric paper test strips to confirm the presence of
cyanide.
Countermeasures
Before cyanide antidote can be administered, the patient must be removed from the cyanide-laden
area, clothing removed, and skin washed with soap and water. If cyanide salts have been ingested,
activated charcoal may prevent absorption from the gastrointestinal tract.
Management of cyanide toxicity is based on the principle of reversing and/or displacing cyanide
binding to cytochrome a3. There are two major modalities of treatment: hydroxocobalamin and
the cyanide antidote kit containing sodium nitrate and sodium thiosulfate.5
• Hydroxocobalamin (Cyanokit): The preferred antidote, based on a 2018 US Food and Drug
Administration (FDA) expert consensus panel, is the Cyanokit, containing lyophilized
hydroxocobalamin and other products used for intravenous infusion. Hydroxocobalamin
contains cobalt, to which cyanide has a strong binding affinity. The reaction of
hydroxocobalamin with cyanide produces cyanocobalamin (vitamin B12) that is then
excreted in the urine.
• Cyanide Antidote Kit: The primary components of these kits include sodium nitrate
and sodium thiosulfate.6 When administered intravenously, sodium nitrate and sodium
thiosulfate release cyanide from cytochrome a3 by providing a target for which cyanide has
a higher attraction. IV sodium nitrate reacts with hemoglobin to cause the formation of
Factsheet
Cyanide
methemoglobin, for which cyanide has a high binding affinity. Sodium thiosulfate provides
a source of sulfur that the enzyme rhodanese—the major pathway for metabolism of
cyanide—utilizes to detoxify cyanide.
Recovery
Although recovery from a chemical attack is rare, victims may survive sub-lethal exposures,
whether from ingestion, smoke inhalation, or exposure to cyanide-containing industrial products.
Patients who are treated successfully for cyanide poisoning should be observed for development
of long-term neuropsychiatric symptoms that are similar to symptoms experienced by survivors of
cardiac arrest or carbon monoxide poisoning.
References
1. Baskin SI, Brewer TG. Cyanide poisoning. In: Zajtchuk R, Bellamy RF, eds. Textbook of Military Medicine:
Medical Aspects of Chemical and Biological Warfare. Washington, DC: US Department of the Army Office
of the Surgeon General; 2001. https://www.hsdl.org/c/abstract/?docid=1018
2. US Centers for Disease Control and Prevention. Facts about cyanide. Updated April 4, 2018. Accessed
November 1, 2022. https://emergency.cdc.gov/agent/cyanide/basics/facts.asp
3. Holstege CP, Kirk MA. Cyanide and Hydrogen Sulfide. In: Nelson LS, Howland M, Lewin NA, Smith SW,
Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw Hill; 2019. Accessed
November 01, 2022. https://accessemergencymedicine.mhmedical.com/book.aspx?bookid=2569
4. Graham J, Traylor J. Cyanide toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
Posted January 2022. Updated February 17, 2022. https://www.ncbi.nlm.nih.gov/books/NBK507796/
5. US Department of Health and Human Services. Cyanide antidotes. Updated September 1, 2022.
Accessed November 1, 2022. https://chemm.hhs.gov/antidote_cyanide.htm
6. Nithiodote: Sodium Nitrate and Sodium Thiosulfate Kit [Package Insert]. Hope Pharmaceuticals.
DailyMed/National Library of Medicine. Updated February 11, 2022. Accessed November 1, 2022.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ff4941b3-9901-4aab-adcf-c5327bede34e

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Factsheet

Updated November 2, 2022

First isolated in 1782, cyanide is a compound composed of carbon atom triple-bonded to a

Use as Chemical Warfare Agent

Mechanism of Action and Toxicokinetics

Signs and Symptoms

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