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Basics

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BASICS

Overview!!navigator!!

  • Nitrate intoxication is primarily a problem in ruminants because of their efficient reduction of nitrate to nitrite within the rumen
  • Monogastrics generally tolerate rather high concentrations of nitrate because it is not rapidly reduced to nitrite in the gastrointestinal tract
  • Nitrite is approximately 3- and 10-fold more toxic than nitrate for ruminants and monogastrics, respectively
  • Nitrate is found in plants, water, fertilizers, and animal wastes
  • Horses are most likely to be intoxicated after exposure to high concentrations of nitrate or nitrite in fertilizers, but no cases of equine nitrate/nitrite intoxication have been published
  • Nitrite converts Fe2+ in hemoglobin to Fe3+, forming methemoglobin, which cannot bind and transport oxygen. In turn, this leads to generalized tissue hypoxia

Signalment!!navigator!!

  • No breed or sex predispositions
  • Neonates may be more sensitive because of their more efficient reduction of nitrate to nitrite, but data are lacking

Signs!!navigator!!

  • Polypnea
  • Dyspnea
  • Cyanotic or muddy mucous membranes
  • Weakness
  • Muscle tremors
  • Reluctance to move
  • Terminal convulsions
  • Death

Causes and Risk Factors!!navigator!!

The most likely cause is acute exposure to a concentrated source of nitrate or nitrite (e.g. fertilizers or contaminated water source); a horse is unlikely to be exposed to sufficient nitrate from other sources such as plants to cause intoxication.

Diagnosis

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DIAGNOSIS

Differential Diagnosis!!navigator!!

Other causes of methemoglobin formation such as Acer rubrum (red maple) toxicosis (clinical signs of icterus and anemia) or chlorate toxicosis (identified source of exposure to a chlorate salt, e.g. potassium or sodium chlorate).

CBC/Biochemistry/Urinalysis!!navigator!!

  • Methemoglobin imparts a brown discoloration to blood
  • All routinely measured parameters are normal

Other Laboratory Tests!!navigator!!

  • Significant methemoglobinemia (>30%)
  • High plasma, serum, or ocular fluid nitrate or nitrite concentrations—diagnostic concentrations have not been determined for horses
  • Measurement of high nitrate/nitrite in an environmental source has been associated with a suspected fertilizer spill

Imaging!!navigator!!

N/A

Other Diagnostic Procedures!!navigator!!

N/A

Pathologic Findings!!navigator!!

No specific postmortem findings except for a dark red to brown discoloration of the blood and muscle as a result of methemoglobin pigmentation.

Treatment

TREATMENT

Treat acidosis and ischemia-induced ECG changes.

Medications

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MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Reduce methemoglobin to hemoglobin
  • The standard treatment for methemoglobinemia is methylene blue, which is not believed to be efficacious in horses (although this conclusion is based on limited data)
  • Ascorbic acid (30 mg/kg BID given in IV fluids) may be beneficial in reducing methemoglobin, but, as with methylene blue, studies of clinical efficacy are lacking

Contraindications/Possible Interactions!!navigator!!

N/A

Follow-up

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FOLLOW-UP

Patient Monitoring!!navigator!!

Monitor methemoglobin concentrations, acid–base status, and ECG.

Prevention/Avoidance!!navigator!!

N/A

Possible Complications!!navigator!!

N/A

Expected Course and Prognosis!!navigator!!

Because methylene blue may not be efficacious, prognosis is guarded.

Miscellaneous

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MISCELLANEOUS

Associated Conditions!!navigator!!

N/A

Age-Related Factors!!navigator!!

More efficient reduction of nitrate to nitrite might occur in neonates.

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

Fetal hypoxia is a concern in pregnant animals.

Suggested Reading

Osweiler GD, Carson TL, Buck WB, Van Gelder GA. Nitrates, nitrites, and related problems. In: Osweiler GD, ed. Clinical and Diagnostic Veterinary Toxicology, 3e. Dubuque, IA: Kendall Hunt Publishing, 1985:460467.

Author(s)

Authors: Arya Sobhakumari and Robert H. Poppenga

Consulting Editors: Wilson K. Rumbeiha and Steve Ensley