Cyanide Toxicity 

Cyanide toxicity is generally considered to be a rare form of poisoning; however, cyanide exposure occurs relatively frequently in patients with smoke inhalation from residential or industrial fires. Cyanide poisoning also may occur in industry, particularly in the metal trades, mining, electroplating, jewelry manufacturing, and radiographic film recovery. It is also encountered in fumigation of ships, warehouses, and other structures. Cyanides are also used as suicidal agents, particularly among health-care and laboratory workers, and they can potentially be used in a terrorist attack. (See Etiology, Presentation, and Treatment.)

Numerous forms of cyanide exist, including gaseous hydrogen cyanide (HCN), water-soluble potassium and sodium cyanide salts, and poorly water-soluble mercury, copper, gold, and silver cyanide salts. In addition, a number of cyanide-containing compounds, known as cyanogens, may release cyanide during metabolism. These include, but are not limited to, cyanogen chloride and cyanogen bromide (gases with potent pulmonary irritant effects), nitriles (R-CN), and sodium nitroprusside, which may produce iatrogenic cyanide poisoning during prolonged or high-dose intravenous (IV) therapy (>10 mcg/kg/min). (See Etiology.)

Industry widely uses nitriles as solvents and in the manufacturing of plastics. Nitriles may release HCN during burning or when metabolized following absorption by the skin or gastrointestinal tract. A number of synthesized (eg, polyacrylonitrile, polyurethane, polyamide, urea-formaldehyde, melamine) and natural (eg, wool, silk) compounds produce HCN when burned. These combustion gases likely contribute to the morbidity and mortality from smoke inhalation.

Finally, chronic consumption of cyanide-containing foods, such as cassava root or apricot seeds,^[1] may lead to cyanide poisoning.

Overall, depending on its form, cyanide may cause toxicity through parenteral administration, inhalation, ingestion, or dermal absorption. (See the chart below.)

Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of, copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.

Effects of cyanide consumption

Chronic consumption of cyanide-containing foods eventually can result in ataxia and optic neuropathy. Defective cyanide metabolism due to rhodanese deficiency may explain development of Leber optic atrophy, leading to subacute blindness. Cyanide also may cause some of the adverse effects associated with chronic smoking, such as tobacco amblyopia. (See Prognosis and Presentation.)

Cyanide affects virtually all body tissues, attaching itself to ubiquitous metalloenzymes and rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores. Cellular metabolism shifts from aerobic to anaerobic, with the consequent production of lactic acid. Consequently, the tissues with the highest oxygen requirements (brain and heart) are the most profoundly affected by acute cyanide poisoning.

Smoke inhalation, suicidal ingestion, and industrial exposures are the most frequent sources of cyanide poisoning.

Smoke inhalation

Studies in France, Sweden, and Scotland, as well as in the United States, have documented smoke inhalation as an important source of cyanide poisoning. Individuals with smoke inhalation from enclosed space fires who have soot in the mouth or nose, altered mental status, or hypotension may have significant cyanide poisoning (blood cyanide concentrations >40 mmol/L or approximately 1 mg/L).

Many compounds containing nitrogen and carbon may produce hydrogen cyanide (HCN) gas when burned. Some natural compounds (eg, wool, silk) produce HCN as a combustion product.

Household plastics (eg, melamine in dishware, acrylonitrile in plastic cups), polyurethane foam in furniture cushions, and many other synthetic compounds may produce lethal concentrations of cyanide when burned under appropriate conditions of oxygen concentration and temperature.

Intentional poisoning

Cyanide ingestion is an uncommon, but efficacious, means of suicide, often involving cyanide salts found in hospital and research laboratories. Not surprisingly, individuals in certain occupations, such as health-care and laboratory workers, are at risk for suicidal ingestion of cyanides.

Industrial exposure

Countless industrial sources of cyanides exist. Cyanides serve an extremely important role in the metal plating and recovery industries. In addition, industry uses cyanides in the manufacture of plastics, as reactive intermediates in chemical synthesis, and as solvents (in the form of nitriles).

Exposure to salts and cyanogens occasionally causes poisonings; however, a significant risk for multiple casualties occurs when these products come into contact with mineral acids because HCN gas is produced. Water contact with the soluble salts (eg, potassium, sodium cyanide) also may liberate HCN.

Iatrogenic exposure

Sodium nitroprusside, when used in high doses or over a period of days, can produce toxic blood concentrations of cyanide. Patients with low thiosulfate reserves (eg, malnourished, postoperative) are at increased risk for developing symptoms, even with therapeutic dosing. Resultant confusion and combativeness initially may be mistaken as intensive care unit (ICU) syndrome (ie, sundowning). Problems may be avoided by coadministration of hydroxocobalamin or sodium thiosulfate.

Ingestion of cyanide-containing supplements

Ingestion of cyanide-containing supplements is rare. Amygdalin (synthetic laetrile, also marketed as vitamin B-17) contains cyanide and can be found in the pits of many fruits, such as apricots and papayas; in raw nuts; and in other plants (lima beans, clover, and sorghum).

The substance was thought to have anticancer properties due to the action of cyanide on cancer cells. However, laetrile showed no anticancer activity in human clinical trials in the 1980s and is not available in the United States,^[2] although it can be purchased on the Internet.

Occurrence in the United States

Cyanide may be a major contributor to the morbidity and mortality observed in approximately 5000-10,000 deaths from smoke inhalation occurring each year in the United States. Suicidal exposures are rarely reported to poison centers; 18 of 242 (2007) and 25 of 238 (2008) cyanide poisoning cases were intentional exposures as reported to the American Association of Poison Control Centers.^{[3, 4]} However, a rapidly fatal suicide from cyanide salts in an adult patient easily might be attributed to sudden death from myocardial infarction, pulmonary embolus, or ventricular dysrhythmia.

Sex- and age-related demographics

Suicide by cyanide poisoning occurs predominantly in males, as does industrial exposure. Leber optic atrophy has shown a very strong male predominance in European studies.

Deliberate ingestion of cyanide occurs mostly in adults. Smoke inhalation and chronic cyanide poisoning affect all ages.

The prognosis in cyanide toxicity is reasonably good if rapid supportive intervention and effective antidotal therapy are provided. Suicidal poisonings tend to have severe outcomes because large doses are often involved.

Morbidity and mortality

According to the American Association of Poison Control Centers Toxic Exposure Surveillance System, 5 of 242 cases in 2007 and 3 of 238 in 2008 were fatal cyanide exposures.^{[3, 4]}

Cyanide induces fatality in seconds to minutes following inhalation or intravenous injection, in minutes following ingestion of soluble salts, or minutes (hydrogen cyanide) to several hours (cyanogens) after skin absorption.

Individuals who survive cyanide poisoning are at risk for central nervous system dysfunction, such as anoxic encephalopathy. Acute and delayed neurologic manifestations (Parkinson-like syndrome, other movement disorders, neuropsychiatric sequelae) have been reported.

Rapid, aggressive therapy consisting of supportive care and antidote administration is lifesaving.

Educate patients using cyanide in their jobs about safe work practices, including the use of personal protective equipment. Certain cyanide compounds are well absorbed dermally; thus, gloves and other forms of skin protection should be worn. Moreover, cyanide compounds should be scrupulously isolated from exposure to acids.

Educate patients with cancer or human immunodeficiency virus (HIV) who might purchase anticancer supplements over the Internet about the possible risks from such medicines, and encourage them to discuss supplement use with their oncologist.

For patient education information, see the First Aid and Emergency Center and the Lung Disease and Respiratory Health Center, as well as Cyanide Poisoning, Smoke Inhalation, and Carbon Monoxide Poisoning.