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Cyanide Fact Sheet



Cyanide is a rapidly acting lethal agent that is limited in its military usefulness by its high LCt50 and high volatility. Death occurs in 6 to 8 minutes after inhalation of a high Ct (concentration). Sodium nitrite and sodium thiosulfate are effective antidotes.


The French used about 4000 tons of cyanide in WWI without notable military success, possibly because the small one- to two-pound munitions used could not deliver the large amounts needed to cause biological effects. Other factors included the high volatility of cyanide (which quickly evaporated and dispersed) and its "all or nothing" biological activity, i.e., it caused few effects below the lethal Ct (this is in contrast to mustard, which causes eye damage at 1% of the lethal amount).

The U.S. maintained a small number of cyanide munitions during World War II (WWII). Japan allegedly used cyanide against China before and during WWII, and Iraq may have used cyanide against the Kurds in the 1980s.

Terms: The term cyanide refers to the anion CN-, or to its acidic form, hydrocyanic acid (HCN). Cyanogen (C2N2) is formed by the oxidation of cyanide ions; however, the term cyanogen has also come to refer to a substance that forms cyanide upon metabolism and produces the biological effects of free cyanide (the term cyanogen is from "cyano" and "gennan," Greek meaning "to produce"). A simple cyanide (HCN, NaCN) is a compound that dissociates to the cyanide anion (CN-) and a cation (H+, Na+). A nitrile is an organic compound that contains cyanide. A cyanogen usually refers to a nitrile that liberates the cyanide anion during metabolism and produces the biological effects of the cyanide anion. Cyanogens may be simple (cyanogen chloride) or complex (sodium nitroprusside).

Cyanides are also called "blood agents," an antiquated term still used by many in the military. At the time of the introduction of cyanide in World War I, the other chemical agents in use caused mainly local effects: riot control agents injured the skin and mucous membranes from direct contact, and phosgene damaged the lungs after inhalation. In contrast, cyanide when inhaled produced systemic effects and was thought to be carried in the blood; hence the term "blood agent." The widespread distribution of absorbed nerve agents and vesicants via the blood invalidates this term as a specific designator for cyanide. Also, the use of "blood agent" for cyanide connotes to some people that the site of action of cyanide is in the blood, an erroneous notion.

Materials of interest as chemical agents are the cyanide hydrogen cyanide (hydrocyanic acid; AC) and the simple cyanogen, cyanogen chloride (CK). Cyanogen bromide was used briefly in World War I, but is of no present interest.

Sources other than military: The cyanide ion is ubiquitous in nearly all living organisms which tolerate and even require the ion in low concentrations. The fruits and seeds (especially pits) of many plants, such as cherries, peaches, almonds, and lima beans, contain cyanogens capable of releasing free cyanide following enzymatic degradation. The edible portion (the roots) of the cassava plant (widely used as a food staple in many parts of the world) is also cyanogenic. The combustion of any material containing carbon and nitrogen has the potential to form cyanide; some plastics (particularly acrylonitriles) predictably release clinically significant amounts when burned. Industrial concerns in the U.S. manufacture over 300,000 tons of hydrogen cyanide annually. Cyanides find widespread use in chemical syntheses, electroplating, mineral extraction, dyeing, printing, photography, and agriculture, and in the manufacture of paper, textiles, and plastics.


The cyanides are in liquid state in munitions, but rapidly vaporize upon detonation of the munitions. The major threat is from the vapor. The liquid toxicity is about that of mustard (see toxicity, below).

The preferred way to deliver cyanide is by large munitions (bombs, large shells), because smaller weapons will not provide the concentrations needed for effects.


Cyanide has a high affinity for certain sulfur compounds (sulfanes, which contain two covalently bonded but unequally charged sulfur atoms) and for certain metallic complexes, particularly those containing cobalt and the trivalent form of iron (Fe3+). The cyanide ion can rapidly combine with iron in cytochrome a3 (a component of the cytochrome aa3 or cytochrome oxidase complex in mitochrondria) to inhibit this enzyme, thus preventing intracellular oxygen utilization. The cell then utilizes anaerobic metabolism, creating excess lactic acid and a metabolic acidosis. Cyanide also has a high affinity for the ferric iron of methemoglobin and one therapeutic strategem induces the formation of methemoglobin to which cyanide preferentially binds.

The small quantity of cyanide always present in human tissues is metabolized at the approximate rate of 17 Fg/kg"min, primarily by the hepatic enzyme rhodanese, which catalyzes the irreversible reaction of cyanide and a sulfane to produce thiocyanate, a relatively nontoxic compound excreted in the urine. (An elevated concentration of thiocyanate in either blood or urine is evidence of cyanide exposure.) The limiting factor under normal conditions is the availability of a sulfane as a substrate for rhodanese, and sulfur is administered therapeutically as sodium thiosulfate to accelerate this reaction. Because of the ability of the body to detoxify small amounts of cyanide via the rhodanese-catalyzed reaction with sulfane, the lethal dose of cyanide is time dependent; that is, a given amount of cyanide absorbed slowly may cause no biological effects even though the same amount administered over a very short period of time may be lethal. In contrast, the LCt50 of each of the other chemical agents, which are not metabolized to the same extent as is cyanide, is relatively constant over time, and a lethal amount causes death whether administered within minutes or over hours.


Toxicities: Cyanide is the least toxic of the "lethal" chemical agents. The LCt50s of AC and CK by inhalation have been estimated to be 2500-5000 mg"min/m3 for AC and about 11,000 mg"min/m3 for CK. LD50s for hydrogen cyanide have been estimated to be 1.1 mg/kg for intravenous administration and 100 mg/kg after skin exposure. The oral LD50s for sodium and potassium cyanide are about 100 and 200 mg/kg respectively.

Cyanide is unique among military chemical agents because it is detoxified at a rate that is of practical importance, about 17 Fg/kg"min. As a result the LCt50 is greater for a long exposure (e.g., 60 min) than for a short exposure (e.g., 2 min).

Effects: The organs most susceptible to cyanide are the central nervous system (CNS) and the heart. Most clinical effects are of CNS origin and are nonspecific.

About 15 seconds after inhalation of a high concentration of cyanide vapor concentration there is a transient hyperpnea followed in 15-30 seconds by the onset of convulsions. Respiratory activity stops two to three minutes later, and cardiac activity ceases several minutes later still, or at about six to eight minutes after exposure.

The onset and progression of signs and symptoms after ingestion of cyanide or after inhalation of a lower concentration of vapor are slower. The first effects may not occur until several minutes after exposure, and the time course of these effects depends on the amount absorbed and the rate of absorption. The initial transient hyperpnea may be followed by a feelings of anxiety or apprehension, agitation, vertigo, a feeling of weakness, nausea with or without vomiting, and muscular trembling. Later, consciousness is lost, respiration decreases in rate and depth, and convulsions, apnea, and cardiac dysrhythmias and standstill follow. Because this cascade of events is prolonged, diagnosis and successful treatment are possible.

The effects of cyanogen chloride include those described for hydrogen cyanide. Cyanogen chloride is also similar to the riot control agents in causing irritation to the eyes, nose, and airways as well as marked lacrimation, rhinorrhea, and bronchosecretions.

Physical Findings: Physical findings are few and non-specific. The two that are said to be characteristic are in fact not always observed. The first is severe respiratory distress in an acyanotic individual. When seen, "cherry-red" skin suggests either circulating carboxyhemoglobin from carbon monoxide poisoning or a high venous oxygen content from failure of extraction of oxygen by tissues poisoned by cyanide or hydrogen sulfide. However, cyanide victims may have normal appearing skin and may even be cyanotic, although cyanosis is not classically associated with cyanide poisoning.

Table: Cyanide (AC and CK)

Effects from vapor exposure

Moderate, from low concentration Transient increase in rate and depth of breathing, dizziness,nausea, vomiting, headache These may progress to severe effects if exposure continues. The time of onset of these effects depends on the concentration, but is often within minutes after start of exposure.

Severe, from high concentration Transient increase in rate and depth of breathing -- 15 seconds

Convulsions -- 30 seconds

Cessation of respiration -- 2-4 minutes

Cessation of heartbeat -- 4-8 minutes

In addition to the above, CK causes intense irritation of the eyes, nose, and airways.

The second classic sign is the odor of bitter almonds. However, about 50% of the population is genetically unable to detect the odor of cyanide.

The casualty may be diaphoretic with normal sized or large pupils. An initial hypertension and compensatory bradycardia are followed by a declining blood pressure and tachycardia. Terminal hypotension is accompanied by bradyarrhythmias before asystole.


Effects begin in 15 seconds following inhalation of a lethal Ct; death ensues in six to eight minutes. The onset of effects following inhalation of lower Cts may be as early as minutes after the beginning of the exposure. After exposure is terminated by evacuation to fresh air or by masking, there is little danger of delayed onset of effects.


Battlefield inhalational exposure to either cyanide or a nerve agent may precipitate the sudden onset of loss of consciousness followed by convulsions and apnea. The nerve agent casualty has miosis (until shortly before death), copious oral and nasal secretions, and muscular fasciculations. The cyanide casualty has normal sized or dilated pupils, few secretions, and muscular twitching but no fasciculations. In addition, the nerve agent casualty may be cyanotic, and the cyanide casualty usually is not cyanotic.


1. An elevated blood cyanide concentration: Mild effects may be apparent at concentrations of 0.5-1.0 Fg/mL, and concentrations of 2.5 Fg/mL and higher are associated with coma, convulsions and death.

2. Acidosis: Metabolic acidosis with a high concentration of lactic acid (lactic acidosis), or a metabolic acidosis with an unexplained high anion gap (if the means to measure lactic acid are not available) may be present. Because oxygen cannot be utilized, anaerobic metabolism with the production of lactic acid replaces aerobic metabolism. Lactic acidosis, however, may reflect other disease states and is not specific for cyanide poisoning.

3. Oxygen content of venous blood greater than normal. This also is because of poisoning of the intramitochondrial respiratory chain and the resulting failure of cells to extract oxygen from arterial blood. This finding is also not specific for cyanide poisoning.


The primary goal in therapy is to remove the cyanide from the enzyme cytochrome a3 in the cytochrome oxidase complex. A complicating factor is the rapidity with which cyanide, particularly inhaled cyanide, causes death.

A secondary goal is to detoxify or bind the cyanide so that it can not reenter the cell to reinhibit the enzyme. A closely associated goal is supportive management.

Methemoglobin has a high affinity for cyanide, and cyanide will preferentially bind to methemoglobin rather than to the cytochrome. Most methemoglobin formers have clinically significant side effects. The nitrites, which were first used to antagonize the effects of cyanide over a century ago, cause orthostatic hypotension, but this is relatively insignificant in a supine casualty. Amyl nitrite, historically the first nitrite used, is an volatile substance formulated in a perle that is crushed or broken for the victim to inhale. In an apneic patient a means of ventilation is necessary.

Another methemoglobin former, sodium nitrite, is formulated for intravenous use. The standard ampule contains 300 mg of the drug in 10 mL of diluent, and this is injected intravenously over a two- to four-minute period.

Detoxification (metabolism) of cyanide is accomplished by the administration of a sulfur-containing compound that combines with cyanide to produce thiocyanate, a relatively non-toxic substance which is rapidly excreted via the kidneys. The hepatic enzyme rhodanese catalyzes the one-way reaction of cyanide and a sulfane to thiocyanate. Sodium thiosulfate is packaged in a 50-mL ampule containing 12.5 grams of the drug. Intravenous injection of all 12.5 grams follows successful completion of the intravenous injection of sodium nitrite. Half of the original dosage of each drug may be repeated if symptoms persist.


An immediate casualty is one who presents within minutes of inhalational exposure with convulsions or the recent onset of apnea, but with circulation intact. Immediate antidote administration will be lifesaving.

A minimal casualty is one who has inhaled less than a lethal amount and has mild effects. The antidotes may reduce his symptoms, but are not lifesaving.

The delayed casualty is one recovering from mild effects or from successful therapy. Generally, it will be hours before full recovery. Evacuation is not necessary, but might be considered until full recovery takes place.

An expectant casualty is apneic with circulatory failure.

Generally, a casualty who has had inhalation exposure and survives long enough to reach medical care will need little care.


Full recovery is usually relatively fast after cyanide intoxication. Those with mild to moderate effects from the agent can usually return to duty within hours, and those successfully treated after severe effects can return within a day.