|Synonyms||cyanide toxicity, hydrocyanic acid poisoning|
|Classification and external resources|
|Specialty||Toxicology, critical care medicine|
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, and certain seeds such as those from apples. 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 B12a) 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
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.
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.
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 during treatment of hypertensive crisis.[specify]
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 some foods such as almonds, apricot kernel, apple seeds, orange seeds, 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.
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.
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.
|Nitrites||The nitrites oxidize some of the hemoglobin's iron from the ferrous state to the ferric state, converting the hemoglobin into methemoglobin.
Cyanide binds avidly to methemoglobin, forming cyanmethemoglobin, thus releasing cyanide from cytochrome oxidase. Treatment with nitrites is not innocuous as methemoglobin cannot carry oxygen, and severe methemoglobinemia may need to be treated in turn with methylene blue.[note 1]
|Thiosulfate||The evidence for sodium thiosulfate's use is based on animal studies and case reports: the small quantities of cyanide present in dietary sources and in cigarette smoke are normally metabolized to relatively harmless thiocyanate by the mitochondrial enzyme rhodanese (thiosulfate cyanide sulfurtransferase), which uses thiosulfate as a substrate. However, this reaction occurs too slowly in the body for thiosulfate to be adequate by itself in acute cyanide poisoning. Thiosulfate must therefore be used in combination with nitrites.|
|Hydroxocobalamin||Hydroxocobalamin, a form (or vitamer) of vitamin B12 made by bacteria, and sometimes denoted vitamin B12a, is used to bind cyanide to form the harmless cyanocobalamin form of vitamin B12.|
|4-Dimethylaminophenol||4-Dimethylaminophenol (4-DMAP) has been proposed[by whom?] in Germany as a more rapid antidote than nitrites with (reportedly) lower toxicity. 4-DMAP is used currently by the German military and by the civilian population. In humans, intravenous injection of 3 mg/kg of 4-DMAP produces 35 percent methemoglobin levels within 1 minute. Reportedly, 4-DMAP is part of the US Cyanokit, while it is not part of the German Cyanokit due to side effects (e. g. hemolysis).|
|Dicobalt edetate||Cobalt ions, being chemically similar to iron ions, can also bind cyanide. One current cobalt-based antidote available in Europe is dicobalt edetate or dicobalt-EDTA, sold as Kelocyanor. This agent chelates cyanide as the cobalticyanide. This drug provides an antidote effect more quickly than formation of methemoglobin, but a clear superiority to methemoglobin formation has not been demonstrated. Cobalt complexes are quite toxic, and there have been accidents reported in the UK where patients have been given dicobalt-EDTA by mistake based on a false diagnosis of cyanide poisoning. Because of its side effects, it should be reserved only for patients with the most severe degree of exposure to cyanide; otherwise, nitrite/thiosulfate is preferred.|
|Glucose||Evidence from animal experiments suggests that coadministration of glucose protects against cobalt toxicity associated with the antidote agent dicobalt edetate. For this reason, glucose is often administered alongside this agent (e.g. in the formulation 'Kelocyanor').
It has also been anecdotally suggested that glucose is itself an effective counteragent to cyanide, reacting with it to form less toxic compounds that can be eliminated by the body. One theory on the apparent immunity of Grigory Rasputin to cyanide was that his killers put the poison in sweet pastries and madeira wine, both of which are rich in sugar; thus, Rasputin would have been administered the poison together with massive quantities of antidote. One study found a reduction in cyanide toxicity in mice when the cyanide was first mixed with glucose. However, as yet glucose on its own is not an officially acknowledged antidote to cyanide poisoning.
|3-Mercaptopyruvate prodrugs||The most widely studied cyanide-metabolizing pathway involves utilization of thiosulfate by the enzyme rhodanese, as stated above. In humans, however, rhodanese is concentrated in the kidneys (0.96 units/mg protein) and liver (0.15 u/mg), with concentrations in lung, brain, muscle and stomach not exceeding 0.03 U/ml. In all these tissues, it is found in the mitochondrial matrix, a site of low accessibility for ionized, inorganic species, such as thiosulfate. This compartmentalization of rhodanese in mammalian tissues leaves major targets of cyanide lethality, namely, the heart and central nervous system, unprotected. (Rhodanese is also found in red blood cells, but its relative importance has not been clarified.)
A different cyanide-metabolizing pathway, 3-mercaptopyruvate sulfurtransferase (3-MPST, EC 126.96.36.199), which is more widely distributed in mammalian tissues than rhodanese, is being explored. 3-MPST converts cyanide to thiocyanate, using the cysteine catabolite, 3-mercaptopyruvate (3-MP). However, 3-MP is extremely unstable chemically. Therefore, a prodrug, sulfanegen sodium (2, 5-dihydroxy-1,4-dithiane-2,5-dicarboxylic acid disodium salt), which hydrolyzes into 2 molecules of 3-MP after being administered orally or parenterally, is being evaluated in animal models.
|Oxygen therapy||Oxygen therapy is not a cure in its own right. However, the human liver is capable of metabolizing cyanide quickly in low doses (smokers breathe in hydrogen cyanide, but it is such a small amount and metabolized so fast that it does not accumulate).
The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate ('Kelocyanor'), as well as several others. Other commonly-recommended antidotes are 'solutions A and B' (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite.
The UK Health and Safety Executive (HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits. It also states that the availability of Kelocyanor at the workplace may mislead doctors into treating a patient for cyanide poisoning when this is an erroneous diagnosis. The HSE no longer recommends a particular cyanide antidote. Qualified UK first aiders are now only permitted to apply oxygen therapy using a bag valve mask, providing they have been trained in its usage.
- On December 5, 2009, a fire in the night club Lame Horse (Khromaya Loshad) in the Russian city of Perm took the lives of 156 people. 111 people died on the spot and 45 later in hospitals. One of the main causes of death was poisoning from cyanide and other toxic gases released by the burning of plastic and polystyrene foam used in the construction of club interiors. Taking into account the number of deaths, this was the largest fire in post-Soviet Russia.[when?]
- On January 27, 2013, a fire at the Kiss nightclub in the city of Santa Maria, in the south of Brazil, caused the poisoning of hundreds of young people by cyanide released by the combustion of soundproofing foam made with polyurethane. By March 2013, 241 fatalities were confirmed.
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- Hydrogen cyanide in the form of Zyklon B was used in German extermination camps during World War II, and especially from March 1942 onwards, when it was first used experimentally to murder Russian prisoners of war at Auschwitz. Use of the poison was scaled up rapidly until custom-built gas chambers (holding up to about 2000 victims) were constructed as part of the new crematoria complex at Auschwitz-Birkenau. There was also a large undressing room next to the gas chamber, and the victims were told to undress and leave their clothes on a numbered peg for collection later. They were told that they would receive a hot shower, and false shower heads were fitted in the ceilings of the gas chambers, so as to maintain the deception. The gas chambers were sealed hermetically to prevent gas leakage. The Zyklon B pellets were then dropped into the chamber via small openings in the roof. When the pellets were exposed to moisture and human heat (as in a closed chamber), they gave off gaseous HCN, which then killed the victims. Workers in the Sonderkommando were employed to remove the corpses from the gas chamber and strip them of any valuables, such as gold teeth, before the bodies were cremated. The gas was used mainly at Auschwitz and Majdanek, but the extermination camps such as Treblinka built earlier used engine exhaust gas, in which carbon monoxide was the toxic component. The gas chambers were either mobile lorries as at Chelmno or specially built chambers as at Sobibor and Belzec. The victims included prisoners of war, Jews from across Europe, Romani gypsies, Poles, ill and disabled people of all nationalities, as well as political prisoners, homosexuals, Jehovah's Witnesses and anyone who opposed the Nazis.
- Hydrogen cyanide gas has also been used for judicial execution in some states of the United States, where cyanide was generated by reaction between potassium cyanide (or sodium cyanide) dropped into a compartment containing sulfuric acid, directly below the chair in the gas chamber.
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.
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), after being accused of conspiring against Hitler; 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 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.
Mining and industrial
- In 2000, a spill at Baia Mare, Romania resulted in the worst environmental disaster in Europe since Chernobyl.
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- John Tawell, a murderer who in 1845 became the first person to be arrested as the result of telecommunications technology.
- Grigori Rasputin (1916; attempted, later killed by gunshot)
- Goebbels children (1945)
- Stepan Bandera (1959)
- Chicago Tylenol murders (1982)
- Ronald Clark O'Bryan (1944–1984)
- Richard Kuklinski (1935–2006)
- Autumn Marie Klein (April 20, 2013), a prominent 41-year-old neuroscientist and physician, died from cyanide poisoning. Klein's husband, Robert J. Ferrante, also a prominent neuroscientist, was convicted of murder and sentenced to life in prison for her death.
- Murder of Mirna Salihin, on 6 January 2016, she died in hospital after drinking a Vietnamese iced coffee at the cafe in the shopping mall in Jakarta, according to the police, cyanide poisoning was the most likely cause of her death.
- Jonestown, Guyana, was the site of a large mass murder-suicide, in which over 900 members of the Peoples Temple drank potassium cyanide–laced Flavor Aid in 1978.
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