INTRODUCTION	Section 2 of 11
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Background: Cyanide is generally considered to be a rare source 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 x-ray film recovery. It is also encountered in fumigation of ships, warehouses, and other structures. Cyanides are also used as suicidal agents, particularly among healthcare and laboratory workers.

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 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 therapy (>10 mcg/kg/min).

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 of smoke inhalation.

Finally, chronic consumption of cyanide-containing foods, such as cassava, may lead to cyanide poisoning.

Overall, depending on its form, cyanide may cause toxicity through parenteral administration, inhalation, ingestion, or dermal absorption.

Pathophysiology: 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.

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.

Frequency:

• In the US: Cyanide may be a major contributor to the morbidity and mortality observed in approximately 5,000-10,000 deaths from smoke inhalation occurring each year in the United States. Suicidal exposures are rarely reported to poison centers; in 2004, 32 of 257 were intentional exposures reported to the American Association of Poison Control Centers. 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.

• Internationally: Studies in France, Sweden, and Scotland, as well as the United States, document 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).

Mortality/Morbidity: According to the American Association of Poison Control Centers Toxic Exposure Surveillance System, in 2004, 8 fatalities occurred out of 257 total cyanide exposures.

• 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 (eg, anoxic encephalopathy, Parkinsonlike syndrome).

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

Sex: 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.

Age: Deliberate ingestion of cyanide occurs mostly in adults. Smoke inhalation affects all ages. Chronic cyanide poisoning affects children and adults.

	CLINICAL	Section 3 of 11
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History: The delay between exposure and onset of symptoms depends on type of cyanide involved, route of entry, and dose. Rapidity of symptom onset, depending on the type of cyanide exposure, occurs in the following order (most rapid to least rapid): gas, soluble salt, insoluble salt, and cyanogens.

Multiple casualties may present after a fire or hazardous materials incident involving cyanides. In some cases, the individuals involved may be experiencing collective hysteria. If physical findings are absent, cyanide poisoning is unlikely. If lactic acidosis is not present, cyanide poisoning has not occurred. Provide supportive care (oxygen) to all individuals presenting because of the event until absence of cyanide poisoning can be verified.

A history of recent depression in the patient with sudden collapse or altered mental status, acidosis, and tachyphylaxis in the ICU patient on nitroprusside should evoke suspicion of the diagnosis.

• General weakness, malaise, and collapse

• Neurologic symptoms (reflect progressive hypoxia)

• Headache, vertigo, dizziness

• Giddiness, inebriation, confusion

• Generalized seizures

• Coma

• Gastrointestinal symptoms - Abdominal pain, nausea, vomiting

• Cardiopulmonary symptoms

• Shortness of breath, possibly associated with chest pain

• Apnea

Physical: Physical findings are generally nonspecific, yet the onset of illness may be dramatic.

• Vital signs are variable.

• Initial bradycardia and hypertension may rapidly give way to hypotension with reflex tachycardia, with resulting final bradycardia and hypotension.

• Tachypnea may generally precede apnea.

• Pulse oximetry may be high and falsely reassuring (oxygen is present in blood as oxyhemoglobin but cannot be effectively used in oxidative phosphorylation).

• General

• Cherry-red skin color (reflecting absent tissue oxygen extraction)

• HEENT

• Soot in the mouth and nose after smoke inhalation, particularly if altered mental status and/or hypotension are present, suggests the possibility of cyanide poisoning.

• Bright red retinal arteries and veins (due to absent tissue oxygen extraction)

• The smell of bitter almonds on the breath suggests exposure (cannot be detected by 60% of the population).

• Cardiopulmonary

• Possible cardiogenic pulmonary edema

• Aspiration can occur with coma.

• Neurologic

• Confusion, drunken behavior, ataxia

• Mydriasis

• Generalized convulsions

• Coma

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

• Smoke inhalation

• Many compounds containing nitrogen and carbon may produce hydrogen cyanide 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, certain occupations, such as healthcare 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.

• Industry utilizes 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 hydrogen cyanide 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 ICU syndrome (ie, sundowning).

• Problems may be avoided by coadministration of hydroxocobalamin or sodium thiosulfate.

• Ingestion of cyanide-containing supplements (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.

• Laetrile has shown no anticancer activity in human clinical trials in the 1980s and is not available in the United States, but it can be purchased on the Internet.