Cyanide poisoning is a form of histotoxic hypoxia because the cells of an organism are unable to use oxygen, primarily through the inhibition of cytochrome c oxidase. Acute hydrogen cyanide poisoning can result from inhalation of fumes from burning polymer products that use Nitrile in their production, such as wool, silk, polyurethane, or vinyl. If cyanide is inhaled it causes 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 victim progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color 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 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.
Treatment of poisoning and antidotes
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.
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 methemoglobinemia needs to be treated in turn with methylene blue.
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.
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).
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.
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.
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 compartmentalizatiion 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 sulfur transferase (3-MPST, EC 188.8.131.52), 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, sulfagene 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 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 night club Lame Horse (Khromaya Loshad) in Russian city Perm took the lives of 156 people. 111 people died on the spot and 45 later in hospitals. One of the main reasons of lethality was cyanide poisoning 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.
Cyanides were 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. Since cyanide works better with higher stomach acidity, it should, in theory, work best with an empty stomach.
In February 1937, the Uruguayan short story writer Horacio Quiroga committed suicide by drinking cyanide in a hospital at Buenos Aires.
In 1937, the famous 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/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.
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 28, 2012, millionaire 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 27, 2013, after being found guilty of statutory sodomy of a 14-year-old female, 48-year-old Steve Parsons ingested a cyanide pill and died shortly after in Maryville, MO.
On July 19, 2012, Urooj Khan, 46, cashed in an Illinois lottery ticket for more than $600,000. After taxes, the winnings amounted to about $425,000. Khan fell ill the next day and was pronounced dead at a hospital. No autopsy was done because, at the time, the Chicago Medical Examiner's Office didn't generally perform them on people 45 and older unless the death was suspicious. The cutoff age has since been raised to 50. After the basic toxicology screening for opiates, cocaine and carbon monoxide came back negative, the death was ruled a result of the narrowing and hardening of coronary arteries. Days after the initial cause of death was released, a relative of Khan's asked authorities to look into the case further. The morgue reopened the case and did more extensive toxicology studies. On March 1, 2013, the Cook County coroner's office confirmed Khan was the victim of cyanide poisoning.
In 1995, a device was discovered in a restroom in the Kayabacho Tokyo subway station, consisting of bags of sodium cyanide and sulfuric acid with a remote controlled motor to rupture them in what was believed to be an attempt by the Aum Shinrikyocult to produce toxic amounts of hydrogen cyanide gas.
In 2003, Al Qaeda reportedly planned to release cyanide gas into the New York City Subway system. The attack was supposedly aborted because there would not be enough casualties.
The Detective Conan manga/anime series has a large number of cases in which the victims are killed by cyanide, with all or most mentioning an 'almond scent' to describe it.
In Roald Dahl's short story "The Landlady", a landlady poisons a young boy named Billy Weaver staying in her Bed and Breakfast with tea that was said to taste suspiciously like cyanide (described as tasting like "bitter almonds"), presumably to stuff him.
In the 1999 Midsomer Murders episode "Judgement Day", the second murder victim is poisoned by cyanide mixed in a glass of wine.
In the 2008 Doctor Who episode "The Unicorn and the Wasp", the Doctor is nearly poisoned by cyanide, but manages to metabolize it and detoxify himself using a combination of proteins, salt, and a shock, plus the advantage of his non-human physiology.
In the Assassin's Creed video game series, Alan Turing was revealed to have been killed by Templars who laced an apple (which he would later eat) with cyanide in an attempt to make it look as if he had committed suicide.
In Nevil Shute's 1957 novel, On The Beach, set in post-nuclear Australia, citizens are given cyanide capsules to kill themselves with rather than suffer the effects of radiation fallout from the nuclear bombs.
Australian author Nevil Shute's 1957 novel about life after nuclear war, On the Beach, gives the scenario of the Australian government giving survivors free cyanide tablets to commit suicide rather than face death from radiation poisoning.
In Ford Maddox Ford's novel "The Good Soldier" one of the main characters, Florence, commits suicide by drinking her phial of "prussic acid" after learning that her lover is having an affair with another woman.
In the film Unknown (2011), Jürgen commits suicide by emptying a bag of sodium cyanide into his coffee, disguised as a packet of sugar.
In the Kannada film Cyanide (2006), which is about the incidents that occurred in the peripheries of Bangalore after the assassination of the former Indian Prime Minister Rajiv Gandhi, the killers of the Prime Minister use cyanide vials to commit suicide to avoid being captured by the police.
In the James Bond filmDr. No (1962), James Bond believes that his cab driver is an enemy agent, and after a fight scene, begins to interrogate the driver, who proceeds to poison and kill himself with cyanide embedded in a cigarette.
In the James Bond film Skyfall (2012), Raoul Silva discusses his failed attempt to commit suicide using a hydrogen cyanide capsule whilst under interrogation. Rather than kill him, the cyanide burned his body internally, forcing him to wear a prosthetic face plate to hide his disfigurement.
Isaac Asimov's short story "Hostess" features an alien race which requires small amounts of hydrogen cyanide in order for their hemoglobin analogues to remain stable. As such, while they do not suffer cyanide poisoning, cyanide withdrawal is, for them, an extremely painful condition similar to slow strangulation.
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