Case study: monensin (Rumensin) toxicity in dairy replacement heifers (Proceedings)

Article

Many dairy producers use Rumensin? (Elanco Animal Health) in dairy heifers as an aid to controlling coccidiosis and for improved feed efficiency. Rumensin? also is approved for use in lactating cows as a tool for improving milk production efficiency. Monensin, the active compound in Rumensin?, has a very wide safety margin for humans and cattle. But, it can be toxic if not fed according to the FDA-approved label. In other species, such as horses, monensin can be extremely toxic.

Many dairy producers use Rumensin® (Elanco Animal Health) in dairy heifers as an aid to controlling coccidiosis and for improved feed efficiency. Rumensin® also is approved for use in lactating cows as a tool for improving milk production efficiency. Monensin, the active compound in Rumensin®, has a very wide safety margin for humans and cattle. But, it can be toxic if not fed according to the FDA-approved label. In other species, such as horses, monensin can be extremely toxic.

Monensin is a carboxylic polyether ionophore produced by a naturally occurring strain of Streptomyces cinnamonensis. The basic cellular function of ionophores is to create a flux of ion transport across cell membranes. Monensin binds to bacterial cell membranes and causes an efflux of potassium from the cell and an influx of hydrogen ions into the cell. Subsequently, the increased hydrogen ions are exported out of the cell either by active transport involving ATP or passively via sodium entry into cells in exchange for hydrogen. In order to maintain inner cell equilibrium, the bacterial cell expends energy. This ultimately results in death or reduced growth of the bacterium. Since gram-negative bacteria have complex outer cell membranes, they are more resistant to the action of ionophores than are gram-positive bacteria. Ionophores, therefore, selectively inhibit gram-positive bacteria rather than gram-negative bacteria. This shift in rumen microbial population is responsible for most of the effects of monensin.

Three general areas of animal metabolism influenced by monensin are energy metabolism, improved nitrogen metabolism, and general digestive effects, including reductions in both bloat and lactic acidosis. Several modes of action have been described including modified volatile fatty acid production, modified feed intake, changes in gas production, modified feed digestibilities, and alterations in both rumen fill and rate of passage. Other effects of monensin include a reduction in 3-methylindole production, a reduction in face fly and horn fly numbers and control of bovine coccidiosis.

The Case

This case report describes a situation of acute monensin toxicity in a Michigan dairy farm. The problem occurred in the summer of 2008 in a group of 264 dairy replacement heifers between the ages of 6 and 14 months. The heifers were housed in a single sloped three-sided barn on a bedded pack. They were fed a totally mixed ration (TMR) consisting of haylage (80%), corn silage (10%), straw (10%) and a mineral/vitamin supplement that was formulated to meet the specific needs of the heifers. Included in the mineral mix was Rumensin® added at a concentration formulated to provide 50 mg/head per day when mixed in the TMR.

The initial sign that something was wrong in this group of heifers was an acute drop in appetite. It was noted by the morning feeder that the heifers had not cleaned up their TMR from the previous day. Not suspecting any major problem, the employee feeding these heifers mixed and fed a new batch of TMR. Again the heifers had no appetite at all, even for the new feed. The feed was being mixed and delivered to the heifers by a relatively new and inexperienced employee who had been on the job for about 3 weeks. Upon being informed of the lack of appetite, the herdsman investigated the feed and how it was mixed and discovered that concentrated Rumensin® 80 was being mixed into the TMR instead of a mineral premix which should contain the Rumensin®. The mineral premix was designed to deliver 50 mg/head perday of monensin when mixed into the TMR. The approved label dose of monensin for replacement heifers is 50 to 200 mg/head per day. The concentrated Rumensin® 80 was being added accidently to the TMR at the same rate as the mineral premix. By calculation, it was estimated that heifers were actually fed 20,000 mg/head per day, or about 400 times the formulated rate.

The Mix-up

Rumensin® is available to provide different concentration of monensin. Rumensin® 80 contains 80 grams/lb of monensin and is designed to be added to TMRs. Rumensin® is often mixed into custom mineral mixes at various concentrations depending on how they are to be delivered (e.g. free choice or mixed into rations). Upon further investigation of this case, it was discovered that the feed supplier had mistakenly delivered a pallet of Rumensin® 80 instead of the mineral premix containing Rumensin® at a much lower concentration. The inexperienced feeder did not recognize the mix-up and incorporated the concentrated Rumensin® 80 into the TMR at the same rate as the mineral mix was to be incorporated.

Diagnosis

Upon discovery of the mix-up, the feed was immediately removed from the feed bunk. Both alfalfa hay and green chop were offered, but the heifers were not interested in either of these feedstuffs. The next day (day 2 after exposure), grassy hay was offered and some of the heifers began to eat. Saturday morning (day 3 after exposure) a dead heifer was discovered in the group, but the others were starting to chew their cuds and looking brighter and more alert. Sunday (day 4 after exposure) two more dead heifers were discovered. It was noted that some of the remaining heifers appeared more lethargic, but most were chewing their cuds. On Monday morning (day 5 after exposure) there were 11 dead heifers. At this point, the herdsman called the herd veterinarian. Based on the history, it was suspected that acute monensin toxicity was the most likely cause of the heifer deaths. Necropsies were conducted and based on recommendations from the Michigan State University Diagnostic Center for Population and Animal Health (DCPAH) and Elanco Animal Health, samples were collected and submitted for diagnostic analysis. Upon necropsy, the primary lesion observed was a "gritty" feel when the heart muscle was cut. This was later confirmed to mineralization deposits in the heart tissue. No other gross abnormalities were noted. Samples were submitted to DCPAH and lesions consistent with monensin toxicity were found in the heart.

Signs of Toxicity

One week after the initial exposure, 35 of 264 heifers had died. Other heifers appeared to be suffering from heart damage as evidenced by brisket edema, bottle jaw (swelling under the jaw), lethargy, and exercise intolerance. Most of these heifers failed to thrive and were eventually culled. Some heifers were not clinically affected and appear normal today. It is assumed that the spectrum of effects observed was related to how much of the ration and monensin individual heifers ingested.

The LD50 (lethal dose in which 50% of exposed cattle will die) of monensin is estimated to be between 10 to 40 mg/lb (20 to 80 mg/kg) BW. Using the lowest LD50 estimate, for a heifer weighing 500 lbs, the dose where 50% of exposed animals would be expected to die would be 5000 mg/head per day. The normal rate that Rumensin® is fed to heifers is 50 to 200 mg/ head per day. In this case, if heifers had even ingested only 25%of their normal daily diet, they would have ingested a potentially lethal dose of monensin. In cattle, the clinical signs of acute monensin toxicity are loss of appetite (24 to 36 h post ingestion), diarrhea, dullness, weakness, loss of balance or stumbling, difficulty breathing, and death within 3 to 14 d after ingestion of the incriminated feed. Monensin causes cell death by disturbing intracellular ion homeostasis and destabilizing cell membranes. Cell damage is most evident in heart and skeletal muscle. Lesions most commonly seen with monensin toxicity in cattle are heart and skeletal muscle degeneration, necrosis and mineralization. Secondary lesions and clinical signs occur from acute heart failure or chronic cardiovascular insufficiency. There is no specific treatment or antidote for monensin toxicity.

Summary

This case illustrates several important points. 1) Some feed ingredients, if fed incorrectly, can be toxic to cattle. Feed ingredients need to be monitored carefully and cautions taken to prevent toxic situations. 2) It is important to monitor feed ingredients when they are delivered, making sure that they are actually what was ordered. 3) Development of and implementation of standard operating protocols can reduce the risk of mistakes occurring. 4) Employee training is essential. Assuming that employees know the differences in different feed ingredients can lead to disaster.

References

Duffield TF, Bagg RN. Use of ionophores in lactating dairy cattle: a review. Can Vet J. 2000;41(5):388-94.

Hall JO. Ionophore use and toxicosis in cattle. Vet Clin North Am Food Anim Pract. 2000;16:497–50.

Gonzalez M, Barkema HW, and Keefe GP. Monensin toxicosis in a dairy herd. Can Vet J. 2005 October; 46: 910–912.

Novilla MN. The veterinary importance of the toxic syndrome induced by ionophores. Vet Hum Toxicol 1992;34:66–70.

Potter EL, VanDuyn RL, Cooley CO. Monensin toxicity in cattle. J Anim Sci 1984 Jun;58:1499-511.

Rumensin® 80 Product Label, http://elms.xh1.lilly.com/rumensin_80_label.pdf (last accessed 4-10-09).

Schelling GT. Monensin mode of action in the rumen. J Anim Sci1984;58:1518-1527.

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