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Horse owners should use pain medications wisely



NC STATE VETERINARY RESEARCHERS DISCOVER NEW ADVERSE EFFECTS ASSOCIATED WITH SYSTEMIC USE OF NSAIDS IN HORSES

RALEIGH, N.C., November 19, 2004—Non-steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of treatment for many painful conditions in horses, including arthritis, laminitis, and colic. Although these drugs are an important component of therapy for these disease syndromes, overuse and misuse of NSAIDs can result in gastrointestinal injury, kidney damage and even death in horses. Researchers at North Carolina State University’s College of Veterinary Medicine have investigated these drugs in horses with colic-related intestinal injury. This research has uncovered previously unknown adverse effects: NSAIDs actually retard healing of damaged gastrointestinal tissue.

NSAIDs are among the most frequently-used and relied-upon medications in equine medicine. Available in tablet, paste and injectable formulations, their use has been extremely important in the treatment of painful conditions in horses for much of the last 25 years. For example, Butazolidin® (phenylbutazone), commonly known as ‘bute,’ and Banamine® (flunixin meglumine) have dominated the treatment of colic and lameness respectively, although newer NSAIDs such as ketoprofen and naproxen have also been used extensively for these conditions. However, because these drugs are absorbed systemically and are transported throughout the body via the bloodstream, they reach unintended targets where they can have adverse effects. Specifically, there is increasing evidence that two organ systems are particularly susceptible to these drugs: the gastrointestinal tract and the kidneys.

Known adverse effects of systemic NSAIDs

It is now widely recognized that NSAIDs can cause side effects in the gastrointestinal tract, such as stomach ulcers and on rare occasion, potentially fatal conditions such as colitis (severe inflammation and injury of the colon). The kidneys may also suffer damage from these drugs, particularly when horses are dehydrated. Although studies have shown that these complications may be caused by excessive doses of NSAIDs, some horses develop adverse effects when given normal doses. For example, in one study reported by Dr. Noah Cohen at Texas A&M University, five horses evaluated for intermittent colic were found to have right dorsal colitis when taken to surgery, and all had been on normal dosages of phenylbutazone from 5-30 days. In other studies, excessive doses of phenylbutazone have been shown to induce a range of adverse effects within a relatively short period of time, including gastric ulcers, colitis, and kidney damage. Therefore, although a uniform recommendation can be made about careful dosing of horses according to the labeled instructions, owners also need to be aware of the possibility of complications even when they follow these directions. Other factors, particularly dehydration, should alert owners to be especially cautious about administration of even low doses of NSAIDs.

New research raises additional concerns

Recent research conducted by Dr. Anthony Blikslager, associate professor of equine surgery, has yielded surprising results and highlights the complexity of NSAID use. Eight horses with intestinal injury of the small intestine were treated with Banamine®, which is very beneficial for controlling pain and reversing some of the systemic effects of absorption of bacterial toxins from the damaged intestine. Surprisingly, the drug slowed down the intestinal repair process as compared to horses which received no Banamine®, although Banamine® did improve the comfort level of the horses. (None of the horses showed colic signs as they all received the alternative narcotic pain medication butorphanol, trade name Torbugesic®.) Banamine® stopped the intestinal lining from re-sealing for at least 18-hours, which could result in increased endotoxin absorption. According to Dr. Blikslager, “This effect was unexpected because Banamine® is used for its ability to reduce the clinical signs of endotoxin absorption. Now, we need to assess the clinical importance of these findings, and look at safer drugs in the NSAID class.”

New diagnostic methods

While ulcers can cause subtle changes in a horse’s performance, the adverse effects caused by NSAIDs can be quite difficult to detect, so owners and veterinarians need to monitor horses closely during administration. Fortunately, new diagnostic tests are becoming available that can help veterinarians detect problems early. Dr. Sam Jones, associate professor of equine medicine at North Carolina State University’s College of Veterinary Medicine has worked with new diagnostic methods that are paving the way for early detection of problems. “Our awareness of the presence of stomach ulcers has increased dramatically with the availability of new endoscopes that are long enough to reach into the stomach,” notes Dr. Jones. “Ultrasound technology similar to that used to scan tendons has been effective in detecting early evidence of colitis. This allows at-risk horses to be monitored closely before a major problem occurs, and the technology can also be used to monitor the recovery process in horses with on-going colitis.”

What can horse owners do?

When using systemic NSAIDs, horse owners should make sure that they use these drugs in the safest manner possible. “The overall goal of pain management therapy should be to use these drugs at the lowest possible dose for the shortest time possible,” said Dr. Blikslager. “We find that sometimes owners use these drugs in an effort to prevent a problem or to improve a horse’s performance without realizing the potential adverse impact to the horse’s health.”

Unfortunately, there are few outward signs of the initial adverse effects caused by systemic NSAIDs. However, if a horse is being treated with a systemic drug like bute for lameness, and becomes uninterested in food and depressed, gastrointestinal damage could be the reason. The next level of severity would involve episodes of colic or diarrhea. Evidence of any of these findings requires immediate veterinary consultation. The veterinarian may be able to give advice over the phone, but more severe clinical signs warrant immediate attention. Treatment may be as simple as reducing the dose of the NSAID, or taking the horse off NSAIDs completely. More intensive testing at a referral center, involving blood analyses, endoscopy and ultrasound may be required to determine the cause of the problem. Above all else, owners should closely follow the instructions provided by their veterinarian, and immediately alert their veterinarian if they think their horse has a problem associated with systemic NSAID administration.

Summary

It is important to note that systemic NSAIDs can be used very successfully, to the point where some horses with chronic lameness receive bute for extended periods of time, typically at a dose such as 1 g once daily. However, even in these horses, it is worth considering giving horses time off from treatment, such as treating only before and after strenuous exercise on a limited number of days per week, or taking the horse off bute periodically to allow organ systems such as the gastrointestinal tract and kidneys to recover.

Drs. Anthony Blikslager and Sam Jones are associate professors of equine surgery and equine Medicine, respectively, in the Department of Clinical Sciences at the College of Veterinary Medicine, North Carolina State University. Their research and outreach efforts are supported by the Colic and Digestive Disease Program at NC State. http://www.cvm.ncsu.edu/docs/ccddp.html.  Email : Anthony_Blikslager@ncsu.edu , Sam_Jones@ncsu.edu

NEW TRENDS IN EQUINE PAIN MANAGEMENT

New trends are becoming apparent in the human and small animal veterinary markets in an attempt to improve the safety of NSAIDs. For instance, Surpass® (diclofenac sodium), a veterinary prescription topical cream that contains one of the traditional NSAIDs, has recently been approved for use in horses with arthritis. By locally applying the drug, it is likely that systemic effects on other organ systems will be avoided. As with all NSAIDs, owners should pay close attention to the instructions given to them by their veterinarian.

The advent of COX-2 inhibitors, which preferentially target inflammation and not normal organ function has dramatically reduced the incidence of ulcers in both people and dogs. At NC State, research is beginning to show the potential for COX-2 inhibitors for treatment of arthritis and colic in horses. For example, one study showed that the canine drug Etogesic® (etodolac), which preferentially inhibits COX-2, was just as effective for treatment of joint inflammation in horses as bute, but etodolac is less damaging than traditional NSAIDs in the colon. The reduced damage to the colon may be short term, however, as studies comparing the COX-2 drug celecoxib to ibuprofen and diclofenac in humans showed there is no difference in GI effect of the drugs when dosed for one year.

The recent withdrawal of the human drug, Vioxx® (refecoxib), a systemic COX-2 inhibitor now associated with adverse cardiovascular effects (increased blood pressure, myocardial infarction and thrombotic stroke), is further evidence that more research is needed to understand the mode of action of these drugs and the role the COX enzymes play. Fortunately, equine veterinarians do not encounter cardiovascular disease nearly as frequently as human physicians treating people. The cardiovascular complications in people appear to result from the presence of COX-2 in the cardiovascular system in patients without inflammation. Horses may well have COX-2 in their cardiovascular system just as people do, but ‘heart attacks’ are very rare in horses, making this less of a consideration in equine medicine. It has also been shown that COX-2 is present in the kidney under normal circumstances in both people and animals. Because of the potential for adverse effects on the kidneys, veterinarians must be cautious with COX-2 inhibitors when they become available in the future.

ONE HORSE OWNER’S EXPERIENCE WITH NSAID TOXICITY

Chandy Christian is the Executive Director of Development and College Relations for North Carolina State University College of Veterinary Medicine (NCSU CVM). She owns a total of four horses, including Blaze, a 16 year-old Quarter Horse/Tennessee Walking Horse cross.

In 2001, Blaze developed clostridial myonecrosis – a very serious systemic infection. Blaze’s treatment included both phenylbutazone (Butazolidin® or bute) and flunixin meglumine (Banamine®) to reduce inflammation and alleviate pain. The drugs were not given at the same time, and were used within normal dosage guidelines at different times during treatment. While recovering from the infection, Blaze had a colic episode diagnosed as a cecal impaction. Mineral oil was administered through a gastric tube and he was given Banamine® and fluids – all standard colic treatments. Several weeks later, Blaze colicked again with similar signs and treatment. When Blaze colicked for the third time, Dr. Sam Jones, DVM and Associate Professor of Equine Medicine at NCSU CVM, used an innovative new ultrasound technique and was able to determine that Blaze was suffering with right dorsal colitis (RDC). RDC is a condition known to be a potential adverse effect of administration of non steroidal anti-inflammatory drugs (NSAIDs). Bute and Banamine® are the two most common NSAIDs used to treat pain and inflammation in horses.

Christian was devastated to learn that Blaze’s chances for survival were 50/50 at best. But neither she nor Blaze was willing to give up. Blaze’s RDC was treated medically – without surgery – and included a special diet, restricted turn out and medication.

“Blaze and I spent so much time fighting this disease that he learned to drink water on my command,” says Christian. Together they beat the odds and Blaze is now a happy, healthy horse. Because of Blaze’s episode of NSAID-induced RDC, he may no longer be given NSAIDs. According to Christian, “I have posted signs at the barn to warn everyone that Blaze must NEVER be given bute, Banamine® or any other NSAID.”

Blaze’s recovery was a success story for all involved with his case at NCSU. His diagnosis and treatment, along with the histories of four other horses, became the subject of a retrospective study published in the Journal of the American Veterinary Medical Association (JAVMA) in 2003. Dr. Jones and his colleagues pioneered the use of ultrasonography to diagnose RDC and Blaze was their landmark case. “Some horses, like some people, are more prone to NSAID sensitivity than others,” notes Dr. Jones. “Any horse suffering from a systemic illness, infection or dehydration may be much more sensitive to NSAID toxicity than it would be under normal circumstances.” Horse owners should be especially alert to clinical signs of NSAID toxicity: low appetite, lethargy, colic pain, dehydration, weight loss and depression. “I hope that our story will be useful to other horse owners and help save the lives of other horses,” says Christian.

Most horse owners keep bute and Banamine® on hand. Bute is given orally for sore muscles, injuries and miscellaneous pain and swelling. Banamine® is generally administered by intramuscular injection, most often for colic pain. As these – and other NSAIDs – are prescription drugs, they should only be used after consultation with a veterinarian. Given the newly recognized dangers of NSAID toxicity, horse owners should watch for any unusual signs and discuss them with their veterinarian.

PRACTICAL GUIDELINES FOR ADMINISTRATION OF SYSTEMIC NSAIDS TO HORSES

Following are seven practical steps horse owners can follow to help ensure horses don’t suffer adverse effects from pain medications.

1. Avoid use of NSAIDs at a higher frequency than intended.

Avoid using Banamine® and bute more than twice per day and avoid using full doses for prolonged periods of time. For example, a full dose of bute (2g twice per day for the average adult horse) should be tapered down to a lower dose within 3-5-days if possible, and certainly by 1-week (for example, 1g twice per day, followed by 1g once per day). Horse owners should pay very close attention to the directions given by the veterinarian (who will have based the dose on the weight of the horse and the medical condition). The veterinarian’s directions may include the details of tapering the dose.

2. Ensure the horse is well hydrated.

Dehydration contributes to adverse effects. Proper hydration of horses can be more difficult in summer months when the horse’s water requirements increase, and in winter months, when horses may refuse to drink icy cold water. This can be partly remedied by providing clean water sources in both the pasture and stall, and providing a salt block. In addition, warming the water during the winter months can be effective in getting horses to drink. Under normal circumstances, a horse should drink approximately 6 gallons of water each day, but a horse’s water requirements increase in the summer months due to sweating. The simplest way to monitor water intake is by seeing how much water is left at the end of the day from a 5-gallon bucket. However, alternate water sources such as a trough in a field make this difficult. Unfortunately, clinical dehydration is not detectable until the horse has lost at least 5% of its body weight in fluid. If concerned about possible dehydration, owners can feel the gums, which should be moist, and can pinch a tent of skin on the neck. The skin should settle back down within approximately 3-seconds. (Note that skin in horses older than 20-years may tent up longer even under normal circumstances).

3. Pay close attention to the horse’s manure output.

A normal horse should produce 6-8 piles of manure daily. A reduction in this amount could mean something as simple as reduced feed intake, but may also be an indication of early problems with the gastrointestinal tract.

4. Contact a veterinarian if the horse has either excessive or minimal urination.

Actual kidney function is very difficult for horse owners to monitor. So-called ‘kidney colic’ is almost always pain associated with the gastrointestinal tract. However, horses that have a major problem with their kidneys may drink and urinate excessively, have blood in their urine, or produce very little urine. Urine color may be an indicator of the horse’s heath, and very dark or reddish urine should be discussed with the attending veterinarian. If there is a question about kidney function, a veterinarian can readily perform urine and blood analyses to screen for kidney problems.

Consider time off from treatment.

If the horse needs bute daily to stay sound and comfortable, consider giving it time off from treatment. This provides a ‘NSAID vacation’ for the GI tract and kidneys, and may prevent NSAID related damage.

Keep a list of all OTC supplements and medications used with the horse and never use multiple pain medications unless directed by a veterinarian.

Just as with human products, interactions can occur between OTC supplements and prescribed veterinary medications. Make certain the attending veterinarian knows everything the horse takes. If the veterinarian prescribes an NSAID for an acute problem or injury, and the horse is also receiving a maintenance dose of another drug for a chronic problem, ask the veterinarian if it is okay to give the second drug.

Consult a veterinarian if any problems possibly associated with drug administration arise, including reduced appetite, diarrhea, or colic.

It’s a good idea to keep notes on the horse’s mood and physical condition any time a new drug regimen is started. Small details may be forgotten and could provide important information to the veterinarian if the horse develops a problem later.

References

Blikslager AT. Consider human NSAIDs to nurse pain in horses. DVM Magazine 2002, September 1, pp. E1-E3.

Moses VS, Bertone AL. Nonsteroidal anti-inflammatory drugs. Vet Clin North Am Equine Pract 2002;18:21-37

Brumbaugh GW. Adverse drug reactions and interactions in the horse.

Vet Clin North Am Equine Pract. 2001;17:445-53

Blikslager AT. Management of pain in horses with colic. Comp Stand Care 2001;1:7-12.

Jones SL, Blikslager AT. The future of anti-inflammatory therapy. Vet Clin North Am Equine Pract 2001;17: 245-262.

Blikslager AT. Do we need cyclooxygenase-2 inhibitors in equine practice? Comp Contin Educ Pract Vet 1999;21:548-550.

Cohen ND, Carter GK, Mealey RH, Taylor TS. Medical management of right dorsal colitis in 5 horses: a retrospective study (1987-1993). J Vet Intern Med 1995;9:272-6.

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