Cyanide

Chapter 86 Cyanide



Erica Lynn Reineke, VMD, DACVECC, Kenneth J. Drobatz, DVM, MSCE, DACVIM, DACVECC



KEY POINTS



• Sources of cyanide poisoning include environmental contamination, smoke inhalation, food sources, and sodium nitroprusside therapy.

• There are no known reports in the veterinary literature of cyanide toxicity from naturally occurring sources in companion animals. However, cyanide poisoning should be suspected in smoke inhalation victims or animals on prolonged infusions of sodium nitroprusside.

• Histotoxic hypoxia is the hallmark of cyanide poisoning, resulting from inhibition of aerobic metabolism.

• Diagnosis of cyanide toxicity typically is based on history, physical examination, and presence of a lactic acidosis. However, whole blood cyanide concentration is considered to be the gold standard for diagnosis.

• Antidotes for cyanide toxicity include intravenous sodium nitrite and sodium thiosulfate. Hydroxycobalamin may also be considered as an adjunctive therapy.

• Any patient receiving sodium nitroprusside therapy who exhibits central nervous system signs, cardiovascular instability, and an increasing metabolic acidosis should be assessed for cyanide toxicity. Sodium nitroprusside therapy should be discontinued immediately and an antidote administered.


INTRODUCTION


Cyanide is readily available and accessible in a variety of forms. Historically, cyanide was used in warfare in the volatile, water-soluble, liquid forms of cyanide and cyanogen chloride.1 Cyanide salts, which produce a cyanide gas when mixed with acid, are used in industrial applications including chemical synthesis, electroplating, tanning, metallurgy, printing, agriculture, photography, manufacturing of paper and plastics, and as fumigants and insecticides. Industrial solvents, as well as artificial nail and glue removers, contain the nitriles, acetonitrile and propionitrile.1 These substances do not contain cyanide, but they are metabolized to cyanide in the liver.1


Cyanide is also found in very low concentrations in foods in the form of amygdalin, a sugar compound with cyanide attached. Once ingested, amygdalin is metabolized to hydrogen cyanide in the gastrointestinal tract. The most well-known source of cyanide in food is the seeds and fruit pits from the Prunus spp (apples, chokecherries, bitter almonds, and apricots). Other food sources known to contain cyanide include lima beans and cassava.1


Another possible source of cyanide exposure is enclosed space fires. Combustion of many substances such as nylon, plastics, wool, and silk may release hydrogen cyanide gas.1 Therefore victims of smoke inhalation are at risk for cyanide poisoning in addition to carbon monoxide poisoning2 (see Chapters 28 and 87, Smoke Inhalation and Carbon Monoxide, respectively).


Finally, cyanide exposure can result from iatrogenic sources. The antihypertensive agent, sodium nitroprusside, can release up to five cyanide groups during its metabolism, and toxicity may develop as cyanide accumulates.1,3


Despite widespread cyanide sources and cyanogenic compound use, there are no known reports of cyanide toxicity from naturally occurring sources in companion animals. However, cyanide toxicity may have contributed to reportedly abnormal mucous membrane color in dogs following smoke inhalation, and to a loss of consciousness and abnormal cardiovascular variables in cats following smoke inhalation.4,5


The hallmark of cyanide poisoning is histotoxic hypoxia due to inhibition of aerobic metabolism.1 This can lead to the “brick-red” mucous membrane color indicative of poor tissue oxygen extraction that has been classically associated with cyanide toxicity. Because of the disruption of cellular respiration, a switch to anaerobic metabolism occurs and results in a significant metabolic acidosis with dramatically elevated lactate concentrations.1 Death from cyanide poisoning can happen quickly; however, antidotes are available and typically are effective if administered in time.



MECHANISMS OF TOXICITY


Cyanide is well known for its high degree of lethality and has been studied extensively in animal models. In a dog model of cyanide poisoning, the lethal dose, or LD50, of potassium cyanide was found to be 2.4 ± 0.2 mg/kg6 and the lethal blood level of cyanide was found to be 438 ± 40 μg/dl.6 This potency is a result of cyanide’s rapid diffusion into tissues and binding to target sites. Intravenous and inhalation exposures to cyanide produce the most rapid onset of signs, within seconds to minutes, and toxicity from ingestion of cyanide or cyanogenic compounds can occur within minutes to hours.1


Cyanides are present in low concentrations in the environment; therefore several intrinsic biochemical pathways for cyanide detoxification exist. The most important route for cyanide excretion is through the formation of thiocyanate, which is subsequently excreted in the urine through the kidneys.1 Thiocyanate is formed primarily in the liver, directly through the activity of the rhodanase enzyme and indirectly via the enzymes 3-mercaptopyruvate sulfurtransferase and thiosulfate reductase.1,3 These enzymes are responsible for combining cyanide and sulfur to form thiocyanate. Despite these intrinsic mechanisms for cyanide detoxification, these enzyme systems are easily overwhelmed during cyanide poisonings because of the body’s limited supply of sulfur (Figure 86-1).1


image

Figure 86-1 Cyanide binds to cytochrome oxidase in the mitochondria, resulting in inhibition of the electron transport chain and loss of aerobic metabolism and generation of adenosine triphosphate. Nitrites react with oxyhemoglobin to form methemoglobin, which draws cyanide out of the mitochondria and forms cyanomethemoglobin. The enzyme rhodanase combines thiosulfate with cyanomethemoglobin to form thiocyanate, which is excreted by the kidneys and eliminated in the urine. Methemoglobin is converted back to oxyhemoglobin by the enzyme methemoglobin reductase.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Cyanide

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