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Cyanide is a highly toxic chemical with a variety of uses, including chemical synthesis, laboratory analysis, and metal plating and polishing. Aliphatic nitriles (acrylonitrile and propionitrile) used in plastic manufacturing are metabolized to cyanide. The vasodilator drug nitroprusside releases cyanide upon exposure to light or through metabolism. Natural sources of cyanide (amygdalin and many other cyanogenic glycosides) are found in apricot pits, cassava, and many other plants and seeds, some of which may be important exposures, depending on ethnobotanical practices. Acetonitrile, a solvent that was a component of some artificial nail glue removers, has caused several pediatric deaths due to conversion to cyanide in the body.
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Hydrogen cyanide gas is generated easily by mixing acid with cyanide salts and also is a common combustion by-product of burning plastics, wool, and many other natural and synthetic products. Hydrogen cyanide poisoning is an important cause of death from structural fires and deliberate cyanide exposure (through cyanide salts) remains an important instrument of homicide and suicide. Hydrogen cyanamide, an agricultural chemical used as a plant regulator, is a potent toxin that inhibits aldehyde dehydrogenase but does not act as a cyanide analog.
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MECHANISM OF TOXICITY
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Cyanide is a chemical asphyxiant, blocking the aerobic utilization of oxygen by binding to cellular cytochrome oxidase.
The bulk of unbound cyanide (80%) is detoxified by metabolism to thiocyanate, a much less toxic compound that is excreted in the urine.
Pharmacokinetic data in humans are limited. Inhalation absorption of gas is almost immediate and oral absorption of salts is rapid (minutes). It has been estimated that in poisoning, 50% of cyanide is found in blood (98% in erythrocytes) and the remainder evenly divided between muscles and all other sites. Based on animal studies, the volume of distribution is approximately 0.8 L/kg and the elimination half-life is 23 minutes (predominantly first-order kinetics prior to sulfur-based detoxification saturation).
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Exposure to hydrogen cyanide gas (HCN), even at low levels (150–200 ppm), can be fatal. The air level considered immediately dangerous to life or health (IDLH, NIOSH) is 25 mg/m3. The Occupational Safety and Health Administration (OSHA) legal permissible exposure limit (PEL) for HCN is 5 mg/m3. The recommended workplace ceiling limit (ACGIH TLV-C) is 4.7 ppm (5 mg/m3 for cyanide salts). Cyanide salts in solution are well absorbed across the skin.
Adult ingestion of as little as 200 mg of the sodium or potassium salt can be fatal. Solutions of cyanide salts are readily absorbed through intact skin.
During nitroprusside infusions at normal rates and durations, cyanide poisoning is relatively rare.
Dietary acute toxicity after ingestion of amygdalin-containing seeds (unless they have been pulverized) is uncommon, but unusual plant sources should be kept in mind. Chronic cyanide toxicity can characterize exposure through dietary sources.
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CLINICAL PRESENTATION
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