Cyanide poisoning
Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have 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 sodium 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 lactic acid. 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 hydrogen 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, dizziness, 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. Despite the similar name, cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5  mg/kg body weight. Other sources claim a lethal dose is 1–3 mg per kg body weight for vertebrates. Chronic exposure. Exposure to lower levels of cyanide over a long period (e.g., after use of improperly processed cassava roots, which are 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. Causes. Acute hydrogen cyanide poisoning can result from inhalation of fumes from burning polymer products that use nitriles 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 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. Flaxseed also contains cyanogenic glycosides, so regular consumption of it may warrant medical advice or treatment. Mechanism . Cyanide is a potent cytochrome "c" oxidase (COX, a.k.a Complex IV) inhibitor. As such, cyanide poisoning is a form of histotoxic hypoxia, because it interferes with oxidative phosphorylation. Specifically, cyanide binds to the heme a3-CuB binuclear center of COX (and thus is a non-competitive inhibitor of it). This prevents electrons passing through COX from being transferred to O, which not only blocks the mitochondrial electron transport chain but also interferes with the pumping of a proton out of the mitochondrial matrix which would otherwise occur at this stage. Therefore, cyanide interferes not only with aerobic respiration but also  with the ATP synthesis pathway it facilitates, owing to the close relationship between those two processes. One antidote for cyanide poisoning, nitrite (i.e. via amyl nitrite), works by converting ferrohemoglobin to ferrihemoglobin, which can then compete with COX for free cyanide (as the cyanide will bind to the iron in its heme groups instead). Ferrihemoglobin cannot carry oxygen, but the amount of ferrihemoglobin that can be formed without impairing oxygen transport is much greater than the amount of COX in the body. Cyanide is a broad-spectrum poison because the reaction it inhibits is essential to aerobic metabolism; COX  is found in many forms of life. However, susceptibility to cyanide is far from uniform across affected species; for instance, plants have an alternative electron transfer pathway available that passes electrons directly from ubiquinone to O, which confers cyanide resistance by bypassing COX. Diagnosis. Lactate is produced by anaerobic glycolysis when oxygen concentration becomes too low for the normal aerobic respiration pathway. Cyanide poisoning inhibits aerobic respiration and therefore increases anaerobic glycolysis which causes a rise of lactate in the plasma. A lactate concentration above 10 mmol per liter is an indicator of cyanide poisoning, as defined by the presence  of a blood cyanide concentration above 40 µmol per liter. Lactate levels greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning, such as cyanide-containing smoke exposure, suggests significant cyanide exposure. Methods of detection include colorimetric assays such as the Prussian blue test, the pyridine-barbiturate assay, also known as the "Conway diffusion method" and the taurine fluorescence-HPLC but like all colorimetric assays these are prone to false positives. Lipid peroxidation resulting in "TBARS," 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. Cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure. Other methods of detection include the identification of plasma lactate. 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. Antidote. 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 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 Irish 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. History. Fires. The República Cromañón nightclub fire broke out in Buenos Aires, Argentina on 30 December 2004, killing 194 people and leaving at least 1,492 injured. Most of the victims died from inhaling poisonous gases, and carbon monoxide. After the fire, the technical institution INTI found that the  level of toxicity due to the materials and volume of the building was 225 ppm of cyanide in the air. A lethal dose for rats is between 150 ppm and 220 ppm, meaning the air in the building was highly toxic. On 5 December 2009, a fire in the night club Lame Horse (Khromaya Loshad) in the Russian city of Perm took the lives of 156 people. Fatalities consisted of 111 people at the site 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 polyurethane foam used in the construction of club interiors. Taking into account the number of deaths, this was the largest fire in post-Soviet Russia. On 27 January 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, 245 fatalities were confirmed. Gas chambers. In early 1942, Zyklon B, which contains hydrogen cyanide, emerged as the preferred killing tool of Nazi Germany for use in extermination camps  during the Holocaust. The chemical was used to murder roughly one million people in gas chambers installed in extermination camps at Auschwitz-Birkenau, Majdanek, and elsewhere. Most of the people who were murdered were Jews, and by far the majority of these murders took place at Auschwitz. Zyklon B was supplied to concentration camps at Mauthausen, Dachau, and Buchenwald by the distributor Heli, and to Auschwitz and Majdanek by Testa. Camps also occasionally bought Zyklon B directly from the manufacturers. Of the 729 tonnes of Zyklon B sold in Germany in 1942–44, 56 tonnes (about eight percent of domestic sales ) were sold to concentration camps. Auschwitz received 23.8 tonnes, of which six tonnes were used for fumigation. The remainder was used in the gas chambers or lost to spoilage (the product had a stated shelf life of only three months). Testa conducted fumigations for the Wehrmacht and supplied them with Zyklon B. They also offered courses to the SS in the safe handling and use of the material for fumigation purposes. In April 1941, the German agriculture and interior ministries designated the SS as an authorized applier of the chemical, and thus they were able to use it without any  further training or governmental oversight. Hydrogen cyanide gas has 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. Suicide. Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide reacts at a higher level with high stomach acidity. Research. Cobinamide is the final compound in the biosynthesis of cobalamin. It has greater affinity for the cyanide than cobalamin itself, which suggests that it could be a better option for  emergency treatment.