Cyanide Poisoning in Animals - Toxicology
Cyanide Poisoning in Animals - Toxicology
Cyanide Poisoning in Animals - Toxicology
MSD MANUAL
Veterinary Manual
Last full review/revision Apr 2021 | Content last modified Jul 2021
Cyanide poisoning results from exposure to a source of cyanide ions (CN-). There are four main syndromes in
animals:
Classical acute cyanide poisoning is when CN- binds to, and inhibits, the ferric (Fe3+) heme moeity form of
mitochondrial cytochrome c oxidase (synonyms: aa3, complex IV, cytochrome A3, EC 1.9.3.1). This blocks the
fourth step in the mitochondrial electron transport chain (reduction of O2 to H2O), resulting in the arrest of
aerobic metabolism, systemic hypoxia, and death from histotoxic anoxia. Tissues that heavily depend on aerobic
metabolism such as the heart and brain are particularly susceptible to these effects. Cyanide also binds to other
heme-containing enzymes, such as members of the cytochrome p450 family, and to myoglobin. However, these
tissue cyanide "sinks" do not provide sufficient protection from histotoxic anoxia. The acute lethal dosage of
hydrogen cyanide (HCN) in most animal species is ~2 mg/kg. Plant materials containing ≥200 ppm of cyanogenic
glycosides are dangerous. Cyanide poisoning is often a component of smoke inhalation poisoning.
Chronic cyanide poisoning-related hypothyroidism is due to disruption of iodide uptake by the follicular thyroid
cell sodium-iodide symporter by thiocyanate, a metabolite in the detoxification of cyanide.
Chronic cyanide and cyanide metabolite (eg, various glutamyl beta-cyanoalanines)-associated neuropathy
toxidromes, which include diseases such as sorghum cystitis ataxia syndrome in horses, as well as various
cystitis ataxia syndromes in cattle, sheep, and goats
Chronic cyanogenic glycoside exposure (notably from Sorghum spp) -associated musculoskeletal teratogenesis
(ankyloses or arthrogryposes) and abortion
Although cyanide levels can be determined in various biological media from poisoned animals, often the most reliable
method of diagnosis is determination of cyanide (and/or cyanide glycoside and/or relevant cyanide metabolite)
concentrations in food and stomach contents. Feed analysis and neurohistopathology are the gold-standard method of
diagnosis of cyanide-associated neuropathy toxidromes. Likewise, feed analysis and fetal pathology are the gold-
standard methods of diagnosis of chronic cyanogenic glycoside-associated teratogenic syndromes.
Lesions
Acute cyanide poisoning: Necropsy personnel may require appropriate personal protective equipment, including
respirators with suitable cartridges. Venous blood is classically described as being "bright cherry red"; however, this
color rapidly fades after death or if the blood is exposed to the atmosphere. Whole blood clotting may be slow or not
occur. Mucous membranes may also be pink initially, then become cyanotic after respiration ceases. The rumen may
be distended with gas; in some cases the odor of “bitter almonds” may be detected after opening. Rumen contents
may provide a positive sodium picrate paper test (or positive results on other rapid cyanide test strip systems). Rumen
gases may provide positive results in cyanide Draeger tube rapid test systems. Agonal hemorrhages of the heart may
be seen. Liver, serosal surfaces, tracheal mucosa, and lungs may be congested or hemorrhagic; some froth may be
seen in respiratory passages. Cyanide also binds to iron (both Fe2+ and Fe3+) present in myoglobin (although this
occurs more slowly than the binding to cytochrome c oxidase and, hence, is not protective); this may result in a
generalized dark coloration of skeletal muscle. Neither gross nor histologic lesions are consistently seen.
Multiple foci of degeneration or necrosis may be seen in the CNS of dogs chronically exposed to sublethal amounts of
cyanide. These lesions have not been reported in livestock.
Chronic cyanide poisoning: Goiter may be present. Cystitis ataxia toxidromes are characterized by opportunistic
bacterial cystitis with or without pyelonephritis and diffuse nerve fiber degeneration in the lateral and ventral funiculi
of the spinal cord and brain stem. Hindlimb urine scalding and alopecia may be present.
For chronic cyanogenic glycoside-associated teratogenic syndromes, Feed analysis and fetal pathologies
Appropriate history, clinical signs, postmortem findings, and demonstration of HCN in rumen (stomach) contents or
other diagnostic specimens support a diagnosis of cyanide poisoning. Veterinarians should be aware of the possible
need to use appropriate personal protective equipment, including a respirator, when collecting samples that may
liberate cyanide gas (eg, rumen contents and rumen gas cap).
A rapid qualitative and presumptive diagnosis can be made by testing representative plant samples or stomach
contents using the picric acid paper test or by collecting rumen gas cap samples by trocarization and testing with a
Draeger cyanide gas detection tube or other cyanide gas detection system. Negative results with such rapid
presumptive tests do not completely exclude the possibility of cyanide poisoning.
Suitable specimens for more sophisticated testing include the suspected food source, rumen/stomach contents,
samples of the rumen gas cap, heparinized whole blood, liver, and muscle. Antemortem whole blood is preferred;
other specimens should be collected as soon as possible after death, preferably within 4 hours. Specimens should be
sealed in an airtight container, refrigerated or frozen, and submitted to the laboratory without delay. When cold
storage is unavailable, immersion of specimens in 1%–3% mercuric chloride has been satisfactory. The rationale for
using liver as a diagnostic sample is that cyanide binds to the Fe3+ form of cytochrome p450 and other heme-
containing metabolic enzymes. The rationale for using skeletal muscle is that cyanide will bind to the iron moiety in
myoglobin.
Measurement of the urinary metabolite of cyanide, thiocyanate, may reveal increased concentrations after cyanide
poisoning.
Hay, green chop, silage, or growing plants containing >220 ppm cyanide as HCN on a wet-weight (as is) basis are very
dangerous as animal feed. Forage containing <100 ppm HCN, wet weight, is usually safe to pasture. Analyses
performed on a dry-weight basis have the following criteria: >750 ppm HCN is hazardous, 500–750 ppm HCN is
suspect, and <500 ppm HCN is considered safe.
Normally expected cyanide concentrations in blood of most animal species are usually <0.5 mcg/mL. Minimal lethal
blood concentrations are ~3 mcg/mL or less. Cyanide concentrations in muscle are similar to those in blood, but
concentrations in liver are generally lower than those in blood. In dogs, whole blood cyanide concentrations may be 4–
5 times greater than serum concentrations because of binding to ferric ions and sequestration in RBCs.
Differential diagnoses include poisonings by:
nitrate or nitrite
urea
organophosphates
carbamates
as well as infectious or noninfectious diseases and other toxidromes that cause sudden death
Treatment, Control, and Prevention of Cyanide Poisoning
in Animals
Immediate treatment with hydroxocobalamin and oxygen
Methylene blue if diagnosis is in doubt (signs are similar to those of nitrate poisoning)
Key Points
Manage grazing and feed conditions for environmental stress to minimize risk, and analyze feed before
allowing consumption.
Hydroxocobalamin plus 100% oxygen should be administered as soon as possible after suspected
cyanide poisoning.
Removal from the source of exposure is the main clinical priority in chronic cyanide-associated
toxidromes.
Prognosis for cases of chronic cyanide poisoning other than those associated with thyroid syndromes is
guarded.