Michelle Arnold, DVM (Ruminant Extension Veterinarian, UKVDL), University of Kentucky (A special thanks to Dr. Jeff Lehmkuhler, UK Beef Extension Specialist, for his valuable input and comments in the development of this article.)
Ionophores have been used for many years in the beef and poultry industries for improved feed efficiency and control of coccidiosis. Generally, ionophores are considered safe and effective in the correct (target) animals receiving the recommended amounts. However, poisonings do occur and are often due to accidental contamination of feed and feed supplements for the wrong species (horses, for example) or errors in feed mixing resulting in excessive concentrations in the diets of cattle. The ionophores approved for use in cattle include monensin (Rumensin®), lasalocid (Bovatec®) and laidlomycin propionate (Cattlyst®). Although all ionophores can be toxic, this article will focus on monensin, simply because more information is available due to its longstanding and widespread use in the cattle industry since the mid-1970s.
In the US, monensin (trade name “Rumensin”- manufactured by Elanco Animal Health) is a feed additive for cattle indicated “for improved feed efficiency, for increased rate of weight gain, and for the prevention and control of coccidiosis caused by Eimeria bovis and Eimeria zuernii”. Monensin is technically considered a “monovalent carboxylic polyether ionophore antibiotic” produced by the fungus Streptomyces cinnamonensis. Although originally developed for poultry, monensin has beneficial health and growth-promoting properties when fed to cattle. In the rumen, monensin decreases the proportions of acetic and butyric volatile fatty acids and increases propionic acid production, the most efficiently utilized of the ruminal fatty acids. It also selectively kills bacteria that produce methane, resulting in less carbon loss and greater energy efficiency. Lastly, it reduces the ruminal degradation of protein, which improves protein utilization. When monensin is used correctly, cattle weight gains can be maintained with less feed, resulting in significant feed savings. Other beneficial effects of feeding monensin to cattle include reduction in bloat (less methane production), less rumen acidosis, and fewer cases of acute respiratory distress syndrome or “fog fever”. When used incorrectly, toxicity caused by an overdose may cause symptoms ranging from decreased feed intake all the way to death due to heart failure. There is no antidote or specific treatment for poisoning due to ionophores except general supportive care. Of primary importance is the recognition of a potential feed problem and removal of suspect feeds until testing can confirm or deny excessive exposure. Unfortunately, samples of feed taken for testing may not represent what the cattle actually ate, especially in cases of incomplete mixing of ingredients. Feed samples should be taken as soon as a problem is suspected and, if possible, from the trough where the animals were fed to get the most accurate picture of what was consumed.
The toxicity of monensin for cattle and other species is well-documented and is known to be dose dependent. Lethal dose (LD) is one way to measure the short-term poisoning potential (acute toxicity) of a material and is usually expressed as the amount of chemical administered in milligrams per kilogram of the body weight of the animal. LD stands for “Lethal Dose” and LD1 is the amount of a material, given all at once, which will cause the death of 1% of a group of animals. The normal safe range used in stocker and feeder calves for increased rate of weight gain and prevention/control of coccidiosis is 50-200 mg/head/day. The LD1 (lethal dose in which 1% of exposed cattle die) of monensin is estimated to be 2.5 mg/lb of body weight. Using this estimate, for a calf weighing 500 lbs, the dose where 1% of exposed animals would be expected to die would be 1250 mg/head/ day. Although this seems difficult to achieve, it is a relatively easy mistake to make, given the very small amount of monensin used (measured in grams) in a ton of feed.
In cattle, the clinical signs of acute monensin toxicity are:
- Loss of appetite, reduced feed intake or completely off feed (24 to 36 hours after consuming a high dose)
- Diarrhea, signs of abdominal pain
- Dullness, lethargy, depression
- Weakness, ataxia, incoordination, loss of balance, stumbling, muscular stiffness
- Difficult, rapid and/or labored breathing
- Recumbency (down) and death usually within 3 to 14 days of the ingestion of the contaminated feed
- Ionophore toxicity will usually involve a recent change in feed supplementation and will generally involve more than one animal with clinical signs
Cattle that recover from the initial poisoning event may die suddenly from heart failure if exercised or stressed. Later development of congestive heart failure can occur as a consequence to an earlier poisoning. With heart failure, cases may look very similar to pneumonia with difficult, labored breathing due to fluid buildup in and around the lungs. Deaths can occur for extended periods after exposure has stopped depending on the severity of the permanent heart damage.
Diagnosis of monensin toxicosis is not a simple task. The clinical signs and lab findings can be mimicked by other ionophores, toxic plants, and vitamin and/or mineral deficiencies that can cause similar types of muscle damage. Cattle that die from ionophore overdoses normally have evidence of heart failure, but it is not uncommon for nothing to be found in an animal that dies very quickly. In the diagnostic lab, typical findings at necropsy associated with monensin toxicosis in cattle are cardiac (heart) and skeletal muscle degeneration that look like pale or yellow areas in the muscle and secondary problems of fluid buildup in the and around the lungs (pulmonary edema) due to the inability of the damaged heart to pump adequately. In addition to examination of a dead animal, samples of the suspected diet must be analyzed as well. One complicating factor which is poorly understood is the interaction of monensin with other compounds (such as use of tiamulin, oleandomycin, chloramphenicol, erythromycin, sulfonamides, or furazolidone) that has also resulted in death, even though monensin was given in the approved range. This is seen more often in other species (poultry and swine) but has been described in cattle, too. One potential reason this occurs is certain types of antibiotics may delay clearance of monensin by the liver, resulting in accumulation to toxic levels. Whatever the case may be, information on tissue and blood concentrations following overexposure to ionophores is lacking which makes a definitive diagnosis challenging.
Careful use, avoidance of overdosing, and reading label recommendations will help prevent the occurrence of adverse effects associated with this class of compounds. One consistent mistake made by many producers is offering a medicated mixing mineral to their cattle free-choice. “Mixing minerals” are designed to be mixed in feed before offering to cattle to control intake. “Free choice” products, on the other hand, are formulated to limit intake and reduce the risk of overconsumption. The feeding directions on the label should be followed and cautions observed (see Figure 1). If mineral feeders are allowed to stay empty for a period of time or the mineral becomes like concrete due to excess moisture, the potential exists for overconsumption of monensin when a new bag of mineral is finally offered. Additionally, excessive rain can dissolve salt forms of minerals which, if leached from the mineral feeders, can increase the concentration of ionophores remaining.
Figure 1: Example of a mixing mineral label. Note the feeding directions include mixing with feed and the caution states not to feed this product undiluted (free-choice).
Important take-home points:
- Some feed ingredients, if given incorrectly, can be toxic to cattle. Feed ingredients need to be monitored carefully and precautions taken to prevent toxic situations. The greatest risk of intoxication occurs when cattle receive a feed containing monensin for the first time because the rumen microflora are not adapted to the new ingredient. The first sign of a problem is feed refusal.
- It is important to monitor feed ingredients when they are delivered and initially fed. Rapid recognition of clinical signs with the introduction of a new feed, followed by the prompt removal of the new feed until testing can be completed, may help avoid more severe consequences and losses.
- Development and implementation of standard operating protocols can reduce the risk of mistakes occurring.
- Employee training is essential. Assuming that employees new to feeding cattle know the differences in feed ingredients and the importance of correct measurement of feed ingredients can lead to disaster. Communicate what employees need to do, why it is important then follow-up, follow-up, and follow-up to insure it is done correctly.
- Minimizing sorting of feed ingredients is critical to ensure consistent intakes. Additionally, sound mixing techniques are necessary to ensure even distribution through the diet. Be careful if offering feed with ionophores that a free-choice medicated mineral is not accessible at the same time.