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.

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.

1. Cyanide is a chemical asphyxiant, blocking the aerobic utilization of oxygen by binding to cellular cytochrome oxidase.
2. The bulk of unbound cyanide (80%) is detoxified by metabolism to thiocyanate, a much less toxic compound that is excreted in the urine.
3. 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).

1. 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.
2. 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.
3. During nitroprusside infusions at normal rates and durations, cyanide poisoning is relatively rare.
4. Dietary acute toxicity after ingestion of intact amygdalin-containing seeds is uncommon but may occur if the seeds have been crushed. Frequent exposure to some dietary sources (eg, cassava) can result in chronic cyanide toxicity (“Konzo”).

Abrupt onset of profound toxic effects shortly after exposure is the hallmark of acute cyanide poisoning. Symptoms include headache, nausea, dyspnea, and confusion. Syncope, seizures, coma, agonal respirations, and cardiovascular collapse ensue rapidly after heavy exposure.

1. A very brief delay may occur if the cyanide is ingested as a salt, especially if it is in a capsule or if there is food in the stomach.
2. Delayed onset (minutes to hours) may occur after ingestion of nitriles and plant-derived cyanogenic glycosides because metabolism to cyanide is required.
3. Chronic neurologic sequelae may follow severe acute cyanide poisoning, consistent with anoxic injury.
4. Neurologic disease associated with chronic dietary exposure to cyanogenic glycosides (prototypically Konzo in cassava-dependent regions of Africa) is etiologically complex, differing in mechanism from acute cyanide poisoning.

Is based on a history of exposure or the presence of rapidly progressive signs and symptoms. Severe lactic acidosis is usually present with substantive exposure. In severe cases the measured venous oxygen saturation may be elevated owing to blocked cellular oxygen consumption. The classic “bitter almond” odor of hydrogen cyanide may or may not be noted, in part because of genetic variability in the ability to detect the smell.

1. Specific levels. Cyanide and thiocyananate determinations are rarely of use in emergency management because they cannot be performed rapidly enough to influence initial treatment. In addition, they must be interpreted with caution because of a variety of complicating technical factors.
   1. Whole-blood levels higher than 0.5-1 mg/L are considered toxic.
   2. Cigarette smokers may have levels of up to 0.1 mg/L.
   3. Rapid nitroprusside infusion may produce levels as high as 1 mg/L, accompanied by metabolic acidosis.
   4. Measurement of exhaled cyanide can theoretically detect over-exposure but this is not a clinically relevant test.
2. Other useful laboratory studies include electrolytes, glucose, lactate, arterial blood gases, mixed venous oxygen saturation, and carboxyhemoglobin (via co-oximetry, in the setting of smoke inhalation).

1. Emergency and supportive measures. Treat all cyanide exposures as potentially lethal.
   1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen.
   2. Treat coma, hypotension, and seizures if they occur.
   3. Gain IV access and monitor the patient's vital signs and ECG closely.
2. Specific drugs and antidotes. There are only two FDA-approved cyanide antidotes in the United States:
   1. Hydroxocobalamin binds and detoxifies free cyanide. It can interfere with multiple serum assays and hemodialysis blood leak detectors. Red chromaturia and skin erythema are nearly universal with treatment; rash is also common.
      1. In acute poisoning, give 5 g of hydroxocobalamin (children: 70 mg/kg) by IV infusion over 15 minutes.
      2. In severe cases, a second dose may be considered.
      3. For prophylaxis of cyanide toxicity from nitroprusside, recommended hydroxocabalamin dosing is 25 mg/h by IV infusion.
   2. Nithiodote () is an older cyanide treatment based on two modalities. Sodium nitrite produces cyanide-scavenging methemoglobinemia while sodium thiosulfate serves as a sulfur donor for cyanide metabolism.
      1. Sodium nitrite injection, 300 mg/10 mL is administered IV at 2.5-5 mL/min (children 0.2 mL/kg of a 3% solution [6 mg/kg or 6-8 mL/m²] not to exceed 300 mg). Caution: Nitrite-induced methemoglobinemia can be extremely dangerous and even lethal. Nitrite should not be given if the symptoms are mild or if the diagnosis is uncertain, especially if concomitant carbon monoxide poisoning is suspected.
      2. Following the sodium nitrite, sodium thiosulfate, 50 mL of a 25% solution (12.5 g) is administered IV (children 1 mL/kg 25% solution [250 mg/kg or 30-40 mL/m²] not to exceed 12.5 g). Thiosulfate is relatively benign. Its use as an adjunct concomitant with hydroxocobalamin is not supported by experimental data.
   3. Amyl nitrite is no longer approved by the FDA for the treatment of cyanide intoxication due to uncertain effectiveness and risk of diversion for abuse.
   4. Dicobalt edetate is used outside the United States to treat cyanide but is associated with multiple adverse side effects.
   5. Hyperbaric oxygen has no proven role in cyanide-poisoning treatment.
3. Decontamination. Caution: Avoid contact with cyanide-containing salts or solutions and avoid inhaling vapors from vomitus (which may give off hydrogen cyanide gas).
   1. Inhalation. Remove victims from hydrogen cyanide exposure and give supplemental oxygen if available. Each rescuer should wear a positive-pressure, self-contained breathing apparatus and, if possible, chemical-protective clothing.
   2. Skin. Remove and isolate all contaminated clothing and wash affected areas with copious soap and water.
   3. Ingestion. Even though charcoal has a relatively low affinity for cyanide, it will effectively bind the doses typically ingested (eg, 100-500 mg).
      1. Prehospital. Immediately administer activated charcoal if it is available and the patient is alert. Do not induce vomiting unless the victim is more than 30 minutes from a medical facility and charcoal is not available.
      2. Hospital. Immediately place a gastric tube and administer activated charcoal, then perform gastric lavage. Give additional activated charcoal after the lavage.
4. Enhanced elimination. There is no role for hemodialysis or hemoperfusion. Hemodialysis may be indicated in patients with renal insufficiency who develop high thiocyanate levels while on extended treatment with thiosulfate or nitroprusside (p 564).