Cyanide

Chapter 40 Cyanide

Kevin T. Fitzgerald, PhD, DVM

“The coward’s weapon, poison.”

• HCN and cyanide salts are used in a variety of common industrial processes.

• For most species, the lethal dose is 2 mg/kg of HCN.

• Cyanide disrupts the ability of cells to use O₂ in oxidative phosphorylation. The net result is histotoxic tissue hypoxia.

• Clinical signs include vomiting, hyperpnea, tachycardia and cardiac arrhythmias, seizures, coma, and apnea.

• Plasma lactate levels and increased anion gap values may be the best indicators of both the presence and severity of cyanide poisoning. Whole blood cyanide levels are available in many humanlaboratories. It may take time to obtain the results, so these tests are often of little use in emergency situations.

• Treatment consists of removing the animal from the source of exposure, initiating supportive measures (100% O₂ and intravenous fluids), decontaminating skin and fur, and, if exposure is certain, administering antidotal therapy.

• The classic bitter almond smell and cherry red blood are rarely seen outside of textbooks.

• Differential diagnoses include poisonings with carbon monoxide or acute solvent inhalation, heart disease, cerebral disease, and cerebral neoplasia.

SOURCES

Small animals may encounter cyanide in a surprisingly broad array of forms. Hydrogen cyanide (HCN) and cyanide salts are used in a wide variety of common industrial processes. Cyanide is used in electroplating techniques, photographic processes, metal cleaning, and gold mining, and hydrogen cyanide gas is used as a fumigant rodenticide. Some fertilizers contain cyanamide. Some coyote traps are still used that fire sodium cyanide baits into the mouths of the animals (i.e., “coyote-getters”). Hydrogen cyanide is also known as prussic acid, and the nitroprussides are used as hypotensive drugs. Combustion of many plastic compounds produces hydrogen cyanide gas. As a result, many smoke inhalation victims suffer from cyanide toxicity and carbon monoxide poisoning.

Cyanogenic compounds (e.g., laetrile, amygdalin from plants, and nitriles) can release cyanide during metabolism, which most commonly occurs in the gut. Naturally occurring cyanogenic glycosides, such as amygdalin, are found in numerous plants. Seeds of apples, plums, cherries, apricots, and the jetberry bush all release cyanide on digestion and are dangerous if the seed capsule is broken. As few as 5 to 25 seeds can cause intoxication. Natural oil of bitter almonds contains 4% hydrogen cyanide. In addition, some species of lima bean contain notable amounts of hydrogen cyanide. The dried root of cassava (i.e., tapioca) contains fairly large amounts of cyanide and can cause poisoning when eaten in large amounts or if it is improperly cooked. Other forms of cyanide include glue-on nail removers containing acetonitrile and acrylonitrile, which are used in the production of synthetic rubber. Isocyanates (e.g., methyl isocyanate, toluene diisocyanate, and others) are potent skin and mucous membrane irritants, but do not release cyanide after absorption.

For large animals, the most important source of cyanide is plant material. Frost-damaged, hail-damaged, or freshly trampled dead or wilted plants are more dangerous than intact specimens. Not until the plant tissue is damaged or starts to decay does the liberation of hydrogen cyanide begin. In humans the vast majority of cyanide poisonings are intentional. Most involve drinking a sodium cyanide–containing insecticide. The second most common cause of cyanide toxicity in people is smoke inhalation. A list of potential sources of cyanide exposure is included in Box 40-1.

TOXIC DOSE

The minimum toxic dose of free hydrogen cyanide and of potassium cyanide given per os in most mammalian species is about 2 mg/kg HCN (Box 40-2).

Box 40-2 Cyanide

Molecular weight	26.02 D
*Airborne*
Immediately fatal	270 ppm
Life threatening	110 ppm
Legal workplace limits	4.7 ppm
*Oral*
Lethal dose	200 mg

TOXICOKINETICS AND MECHANISM OF TOXICITY

The kinetics of cyanide are not well understood. Cyanide disrupts the ability of cells to use oxygen in oxidative phosphorylation. It does this by binding with the ferric (Fe⁺³) iron of the mitochondrial cytochrome oxidase system. As a result, a shift to anaerobic metabolism occurs, a decrease in adenosine triphosphate (ATP) synthesis ensues, and depletion of cellular energy stores and greatly increased lactic acid production follow, causing an anion gap metabolic acidosis. The net effect is a histotoxic tissue hypoxia. In dogs whole blood cyanide levels may be four or five times greater than serum levels because of the concentration of cyanide in erythrocytes. The elimination half-life (T_½) in dogs is 19 hours. The toxic step defining acute cyanide poisoning is that oxygen released by oxyhemoglobin cleavage can no longer be bound. As a result, blockage of cellular respiration results, and respiratory arrest follows within a few minutes. In addition to the development of tissue hypoxia, it has been shown that cyanide also exhibits direct toxic action on cellular membranes, resulting in their necrosis.

CLINICAL SIGNS

The clinical signs of cyanide poisoning depend on the dose, route of exposure, and time elapsed since exposure. The primary manifestations of intoxication from cyanide-containing compounds are rapid tachypnea, hypotension, and convulsions leading to coma. Severe acute cyanide poisoning progresses rapidly from convulsions to coma to shock to respiratory failure to death. The process is faster with inhalation than with ingestion. Animals with inhalation exposure in enclosed spaces may lose consciousness after only a few breaths, and death follows rapidly within 1 to 15 minutes. Clinical signs may not develop for up to 30 minutes to 1 hour after exposure in animals ingesting amounts large enough to be fatal. Delayed onset of clinical signs (as late as 12 hours) occurs following ingestion of cyanide-containing compounds, such as laetrile, amygdalin, and the nitroprussides.

Chronic poisoning with cyanide is far less common than acute intoxication. Repeated inhalation of small amounts of cyanogen chloride causes dizziness, hoarseness, conjunctivitis, weakness, loss of appetite, and weight loss. Chronic ingestion of cyanide-containing cassava is reported to cause tropical ataxic neuropathy in people, and chronic ingestion of cyanide-containing fertilizer by animals has been reported to cause neurological signs.

It has been often stated in previous references that dermal exposure can lead to systemic cyanide intoxication. However, it is difficult to document actual reported cases of poisoning from dermal exposure other than in animals with total body exposure in confined spaces in which inhalation and ingestion also undoubtedly occurred.

In small animals that do not display sudden collapse, the initial signs may resemble anxiety or hyperventilation. Early signs include tachycardia, hyperpnea, and dyspnea. Later signs of cyanide poisoning are nausea and vomiting, hypotension, generalized seizures, coma, apnea, dilated pupils (either sluggish or totally nonreactive), and a host of cardiac effects, including tachycardia, bradycardia, ventricular arrhythmias, erratic supraventricular arrhythmias, ischemic changes on electrocardiography, atrioventricular blocks, and eventual asystole (Box 40-3).

Tags: Small Animal Toxicology

Sep 11, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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