Abstract

Cyanide poisoning is poisoning that results from exposure to a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms is usually within a few minutes. If a person survives, there may be long-term neurological problems.

Toxic cyanide-containing compounds include hydrogen cyanide gas and a number of cyanide salts. Poisoning is relatively common following breathing in smoke from a house fire. Other potential routes of exposure include workplaces involved in metal polishing, certain insecticides, the medication nitroprusside, and certain seeds such as those of apples and apricots. Liquid forms of cyanide can be absorbed through the skin. Cyanide ions interfere with cellular respiration, resulting in the body's tissues being unable to use oxygen.

Diagnosis is often difficult. It may be suspected in a person following a house fire who has a decreased level of consciousness, low blood pressure, or high blood lactate. Blood levels of cyanide can be measured but take time. Levels of 0.5–1 mg/L are mild, 1–2 mg/L are moderate, 2–3 mg/L are severe, and greater than 3 mg/L generally result in death.

If exposure is suspected, the person should be removed from the source of exposure and decontaminated. Treatment involves supportive care and giving the person 100% oxygen. Hydroxocobalamin (vitamin B12) appears to be useful as an antidote and is generally first-line. Sodium thiosulphate may also be given. Historically cyanide has been used for mass suicide and by the Nazis for genocide.

Signs and symptoms | Acute exposure

If cyanide is inhaled it can cause a coma with seizures, apnea, and cardiac arrest, with death following in a matter of seconds. At lower doses, loss of consciousness may be preceded by general weakness, giddiness, headaches, vertigo, confusion, and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the person progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color that changes to dark may be present as the result of increased venous hemoglobin oxygen saturation. Cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5 mg/kg body weight.

Signs and symptoms | Chronic exposure

Exposure to lower levels of cyanide over a long period (e.g., after use of improperly processed cassava roots as a primary food source in tropical Africa) results in increased blood cyanide levels, which can result in weakness and a variety of symptoms, including permanent paralysis, nervous lesions, hypothyroidism, and miscarriages. Other effects include mild liver and kidney damage.

Cause

Acute hydrogen cyanide poisoning can result from inhalation of fumes from burning polymer products that use nitrile in their production, such as polyurethane, or vinyl. It can also be caused by breakdown of nitroprusside into nitric oxide and cyanide. Nitroprusside may be used during treatment of hypertensive crisis.

In addition to its uses as a pesticide and insecticide, cyanide is contained in tobacco smoke and smoke from building fires, and is present in many seeds or kernels such as those of almonds, apricots, apples, oranges, and in foods including cassava (also known as yuca or manioc), and bamboo shoots. Vitamin B12, in the form of hydroxocobalamin (also spelled hydroxycobalamin), may reduce the negative effects of chronic exposure, and a deficiency can lead to negative health effects following exposure.

Mechanism

Cyanide poisoning is a form of histotoxic hypoxia because the cells of an organism are unable to create ATP, primarily through the inhibition of the mitochondrial enzyme cytochrome c oxidase. Cyanide is quickly metabolized to 2-amino-2-thiazoline-4-carboxylic acid and thiocyanate with a half life of 10–30 minutes as a detoxifying mechanism. Within a few hours of single ingestion, no cyanide can be detected, since all of it is metabolized unless death occurs first. (The detection of cyanide long after supposed ingestion is an indication of a false positive in the diagnostics.) Thiocyanate has a long half life of >24hrs, and is typically eliminated through the kidneys. Thiocyanate is ~1/100th the toxicity of the cyanide parent molecule.

Diagnosis

Old methods of detection involve colorimetric assays such as the Prussian Blue test, the pyridine-barbiturate assay and the taurine fluorescence-HPLC but like all colorimetric assays these can be prone to false positives. Lipid peroxidation, an artifact of heart attack produces dialdehydes that cross-react with the pyridine-barbiturate assay. Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide detection is identical to the assay used to detect glutathione in spinal fluid. Recently, cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has such a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure.

Treatment | Decontamination

Decontamination of people exposed to hydrogen cyanide gas only requires removal of the outer clothing and the washing of their hair. Those exposed to liquids or powders generally require full decontamination.

Treatment | Antidote

The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous sodium thiosulfate. Hydroxocobalamin is newly approved in the US and is available in Cyanokit antidote kits. Sulfanegen TEA, which could be delivered to the body through an intra-muscular (IM) injection, detoxifies cyanide and converts the cyanide into thiocyanate, a less toxic substance. Alternative methods of treating cyanide intoxication are used in other countries.

History | War

Cyanide was stockpiled in chemical weapons arsenals in both the Soviet Union and the United States in the 1950s and 1960s. However, as a military agent, hydrogen cyanide was not considered very effective, since it is lighter than air and needs a significant dose to incapacitate or kill.

History | Suicide

Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide reacts at a higher level with high stomach acidity.

- In February 1937, the Uruguayan short story writer Horacio Quiroga committed suicide by drinking cyanide in a hospital at Buenos Aires.

- In 1937, polymer chemist Wallace Carothers committed suicide by cyanide.

- In the 1943 Operation Gunnerside to destroy the Vemork Heavy Water Plant in World War II (an attempt to stop or slow German atomic bomb progress), the commandos were given cyanide tablets (cyanide enclosed in rubber) kept in the mouth and were instructed to bite into them in case of German capture. The tablets ensured death within three minutes.

- Cyanide, in the form of pure liquid prussic acid (a historical name for hydrogen cyanide), was the favored suicide agent of the Third Reich. It was used to commit suicide by Erwin Rommel (1944), Adolf Hitler's wife, Eva Braun (1945), and by Nazi leaders Heinrich Himmler (1945), possibly Martin Bormann (1945), and Hermann Göring (1946).

- It is speculated that, in 1954, Alan Turing used an apple that had been injected with a solution of cyanide to commit suicide after being convicted of having a homosexual relationship —illegal at the time in the UK—and forced to undergo hormonal castration.

- Members of the Sri Lankan LTTE (Liberation Tigers of Tamil Eelam, whose insurgency lasted from 1983 to 2009), used to wear cyanide vials around their necks with the intention of committing suicide if captured by the government forces.

- On November 18, 1978, Jonestown. A total of 909 individuals died in Jonestown, all but two from apparent cyanide poisoning, in an event termed "revolutionary suicide" by Jones and some members on an audio tape of the event and in prior discussions. The poisonings in Jonestown followed the murder of five others by Temple members at Port Kaituma, including United States Congressman Leo Ryan, an act that Jones ordered. Four other Temple members committed murder-suicide in Georgetown at Jones' command.

- On June 6, 1985, serial killer Leonard Lake died in custody after having ingested cyanide pills he had sewn into his clothes.

- On June 28, 2012, Wall Street trader Michael Marin ingested a cyanide pill seconds after a guilty verdict was read in his arson trial in Phoenix, AZ; he died minutes after.

- On June 22, 2015, John B. McLemore, an horologist and the central figure of the podcast S-Town, died after ingesting cyanide.

- On November 29, 2017, Slobodan Praljak died from drinking potassium cyanide, after being convicted of war crimes by the International Criminal Tribunal for the former Yugoslavia.