section name header

Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • Horses are exquisitely sensitive to ionophore toxicity
  • Ingestion of ionophores can result in a physicochemical and/or pathologic disruption of cardiac muscle, skeletal muscle, nerves, liver, and kidney
  • All ionophores should be considered toxic with similar clinical effects. The LD50 doses for monensin, lasalocid, and salinomycin are 2–3 mg/kg, 21.5 mg/kg, and 0.6 mg/kg body weight, respectively

Pathophysiology!!navigator!!

  • Ionophores are used as growth promoters in cattle and coccidiostats for poultry
  • Ionophores transport ions across the membrane, down concentration gradients, resulting in the loss of ionic gradients across the membranes of excitable cells (muscle and nervous) as well as across the mitochondrial membrane
  • Monensin has a higher affinity for sodium than potassium ions, whereas salinomycin has higher affinity for potassium than sodium ions. Lasalocid binds to calcium and magnesium ions
  • For each ion transported into a cell, another ion is transported out. Loss of the ion gradients across the mitochondrial membrane prevents oxidative metabolism
  • Loss of intracellular potassium suppresses ATP production and decreases cell energy production; increases in intracellular sodium lead to water influx and mitochondrial swelling; ionophores potentiate intracellular calcium influx, and all of these effects contribute to cell death
  • Clinical effects and fatality rates are influenced by the quantity of ionophore ingested:
    • With large amounts, the progression can be extremely rapid with death ensuing within 1–15 h. Lesions may not be found in horses that experience SCD
    • With lesser amounts, signs and pathologic abnormalities related to skeletal and cardiac myopathy are observed. Cardiomyopathy can occur weeks or months later

Systems Affected!!navigator!!

  • Cardiovascular—mitochondrial damage results in myocardial necrosis. Loss of ion gradients alters the polarity of the excitable tissues. Cardiac function, including conductance through the heart muscle, is altered. Connective tissue replaces necrotic myocardial cells, resulting in permanent myocardial dysfunction
  • Musculoskeletal—often similar but less severe damage to skeletal muscle. Muscle fibrosis can occur
  • Nervous—nerve and muscle conduction can be altered, resulting in altered reflexes and muscle coordination
  • Renal/urologic—renal tubular damage associated with myoglobin casts can be seen
  • Hepatobiliary—hepatocellular necrosis and decreased function can occur
  • GI—diarrhea often occurs

Incidence/Prevalence!!navigator!!

Ionophore poisoning still occurs, in spite of increased awareness.

Signalment!!navigator!!

No breed, age, or sex predilections.

Signs!!navigator!!

General Comments

The severity and speed of onset reflect the amount of ionophore ingested.

Historical Findings

  • Multiple horses can be affected
  • Feed refusal, colic, ataxia, weakness, and recumbency are early signs

Physical Examination Findings

  • SCD
  • Tachycardia
  • Cardiac arrhythmias
  • Tachypnea
  • Muscle weakness and ataxia
  • Profuse sweating
  • Epistaxis
  • Signs of CHF
  • Exercise intolerance

Causes!!navigator!!

Accidental contamination of feed at feed mills, in feed trucks, or when horses inadvertently gain access to cattle or poultry feed.

Risk Factors!!navigator!!

Vitamin E and/or selenium deficiency can predispose to more severe tissue damage, but adequate concentrations do not prevent toxicosis.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Acute GI diseases
  • Acute neurologic diseases
  • Rhabdomyolysis
  • Vitamin E/selenium deficiency
  • Viral, bacterial, or other toxic forms of myocardial failure

CBC/Biochemistry/Urinalysis!!navigator!!

  • Increased serum activity of creatine kinase, aspartate aminotransferase, and lactate dehydrogenase
  • Increased blood urea nitrogen and indirect bilirubin concentrations
  • Hyperglycemia
  • Hypocalcemia, hypokalemia, hypomagnesemia, and hypochloremia
  • Myoglobinuria

Other Laboratory Tests!!navigator!!

  • Elevated cardiac troponin I or cardiac troponin T; if normal, does not rule out ionophore toxicosis
  • Blood lactate can be increased

Imaging!!navigator!!

ECG

Paroxysmal or sustained supraventricular and/or ventricular arrhythmias can be present.

Echocardiography

Echocardiographic abnormalities range in severity and include:

  • Dilation of the left and/or right ventricle with possible rounded apices
  • Regional or generalized hypokinesis or dyskinesis
  • Decreases in fractional shortening
  • Marked spontaneous contrast
  • Increases in the mitral E-point—septal separation
  • Increased pre-ejection period and decreased left ventricular ejection period
  • Flattening of the aortic root, reduced aortic root diameter
  • Mild pericardial effusion

Thoracic Ultrasonography

With pulmonary edema, peripheral pulmonary irregularities (B-lines, previously known as comet-tail artifacts) are visible.

Thoracic Radiography

Possible pulmonary edema.

Other Diagnostic Procedures!!navigator!!

  • Radiotelemetric ECG monitoring—for real-time ECG when unstable cardiac rhythms present
  • Continuous 24 h Holter monitoring—for identifying intermittent or paroxysmal cardiac arrhythmias, quantifying numbers of premature complexes, and assessing response to therapy
  • Exercising ECG—for characterization of exercise-induced cardiac arrhythmias and their clinical significance. This should be undertaken 4 months after exposure in horses that have shown minimal signs
  • Toxicology—stomach contents and feedstuffs should be analyzed for ionophores. Monensin has been found in highest concentrations in the heart. Blood, serum, liver tissue, and urine can all be used to confirm exposure

Pathologic Findings!!navigator!!

  • No lesions with SCD
  • Heart and skeletal muscle—vacuolation, swollen mitochondria, lipid vesicles, hypereosinophilia, pyknosis, mineralization, and loss of fiber striation progressing to myocardial fibrosis and chamber dilation with chronicity
  • Nervous system—polyneuropathy of peripheral nerves with axonal degeneration and neuronal vacuolation
  • Additional findings—widespread petechial hemorrhages in the lungs, heart, GI tract, and spleen. Pleural and peritoneal effusion, pulmonary edema, and peripheral edema can occur

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

  • No specific antidote
  • Prevent further toxin absorption
  • Supportive therapy is aimed at restoration of cardiac output and improved tissue perfusion, stabilization of cell membranes, and antiarrhythmic therapy if unstable, life-threatening arrhythmias are present

Appropriate Health Care!!navigator!!

  • Severely affected cases should be hospitalized
  • Mildly affected cases should be rested and the degree of cardiac damage determined

Nursing Care!!navigator!!

  • Continuous ECG monitoring if the cardiac rhythm is unstable
  • Horses should be kept quiet and not moved if cardiac output is low
  • Severely ataxic horses may benefit from head protectors, bandaging, and housing in a padded area

Activity!!navigator!!

  • Horses should be stall rested for up to 4 months, if possible. An echocardiogram and exercising ECG should then be performed to identify persistent cardiomyopathy
  • Although caution is advised, if these tests are normal, the horse can be returned successfully to performance

Diet!!navigator!!

Vitamin E and selenium have been effective as a pretreatment in cattle and pigs. However, their efficacy after exposure to ionophores has not been established.

Client Education!!navigator!!

  • Ionophore toxicosis can have significant medicolegal implications. The client should make detailed records of events leading up to the onset of signs and to have these corroborated by third parties, if possible
  • Horses that are clinically normal post exposure are at risk for developing cardiac compromise later. An echocardiogram performed at the time of diagnosis should identify the horses at risk. The horses should not be used for riding activities for 4 months. After this time, an echocardiogram and exercising ECG should be performed to identify persistent cardiomyopathy

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Gastric lavage with activated charcoal and a saline cathartic, administered by nasogastric tube, can reduce further absorption of the toxin
  • IV fluid therapy should be used with care as it can exacerbate pulmonary edema if acute myocardial failure is present
  • Thiamine (0.5–5.5 mg/kg IM), vitamin E (up to 20 IU/kg daily PO), and selenium (0.01 mg/kg IM) might promote stabilization of cell membranes
  • Antiarrhythmic drugs—see chapters Supraventricular arrhythmias and Ventricular arrhythmias

Contraindications!!navigator!!

  • Digoxin acts synergistically with ionophores through inhibition of Na+,K+-ATPase and increases in cellular calcium influx, promoting cell death
  • Chloramphenicol, sulfonamides, and macrolides can also potentiate ionophore toxicity

Precautions!!navigator!!

All antiarrhythmic drugs can be proarrhythmic. The ECG should be monitored continuously during antiarrhythmic therapy.

Possible Interactions!!navigator!!

See Contraindications.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Acutely, frequent assessment of heart and respiratory rate, pulse quality, blood pressure, blood lactate concentrations, and continuous ECG monitoring are indicated.

Prevention/Avoidance!!navigator!!

Feed manufacturers must take every precaution to ensure that ionophores are not accidentally included in equine feeds.

Possible Complications!!navigator!!

CHF can occur in horses that survive the initial stages.

Expected Course and Prognosis!!navigator!!

  • Mortality varies widely. The amount of ionophore ingested varies markedly. The bitter taste may deter many horses, particularly if they have access to alternative feed sources
  • Some asymptomatic horses develop CHF, whereas others may have decreased cardiac function that is performance limiting

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Pregnancy/Fertility/Breeding!!navigator!!

There is a high risk of fetal compromise if mares develop low cardiac output during pregnancy.

Synonyms!!navigator!!

  • Monensin toxicosis
  • Salinomycin toxicosis
  • Lasalocid toxicosis

Abbreviations!!navigator!!

  • CHF = congestive heart failure
  • GI = gastrointestinal
  • LD50 = median lethal dose
  • SCD = sudden cardiac death

Suggested Reading ⬆ ⬇

Bautista AC, Tahara J, Mete A, et al. Diagnostic value of tissue monensin concentration in horses following toxicosis. J Vet Diagn Invest 2014;26:423–427.

Decloedt A, Verheyen T, De Clerq D, et al. Acute and long-term cardiomyopathy and delayed neurotoxicity after accidental lasalosid poisoning in horses. J Vet Intern Med 2012;26:1005–1011.

Hall JO. Feed-associated toxicants: ionophores. In: Plumless KH, ed. Clinical Veterinary Toxicology. St. Louis, MO: Mosby, 2004:120–127.

Hughes KJ, Hoffman KL, Hodgson DR. Long term assessment of horses and ponies post exposure to monensin sodium in commercial feed. Equine Vet J 2009;41:47–52.

Peek SF, Marques FD, Morgan J, et al. Atypical acute monensin toxicosis and delayed cardiomyopathy in Belgian draft horses. J Vet Intern Med 2004;18:761–764.

Author(s) ⬆

Authors: Virginia B. Reef and Jeffery O. Hall

Consulting Editors: Celia M. Marr and Virginia B. Reef

Acknowledgment: The authors acknowledge the prior contribution of Celia M. Marr.