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Endocrinopathic Laminitis Manuka Honey is the Sweet Spot for Wound Healing Is Intense Exercise Fatal to Racehorses? Technician Update: Stallion With Tetanus
Vol 8 Issue 6 2018
TABLE OF CONTENTS
4 Endocrinopathic Laminitis Cover photo: Shutterstock/geno4ka01
Sweet Success: Manuka Honey Helps Heal Distal Limb Wounds.............................12 TECHNICIAN UPDATE
Stallion With Suspected Tetanus............................................................................................16 NEWS
Incisional Contamination Unlikely to be Cause of SSIs............... 3 Is Intense Exercise Fatal to Racehorses?..............................................15 New Video Series by Dr. Sue Dyson....................................................19
ADVERTISERS Shanks Veterinary Equipment..................................3 Standlee Premium Western Forage......................... 5 Boehringer Ingelheim/Gastroguard....................... 7
Merck Animal Health................................................11 Boehringer Ingelheim/Marquis..............................13 AAEVT............................................................................17
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Incisional Contamination Unlikely to to Be Sole Cause SSIs
Courtesy of the Equine Vet Journal
Contamination of the incision alone is unlikely to be the cause of surgical site infections (SSIs) in horses undergoing exploratory laparotomy, according to a recent U.K. study. The researchers wanted to know what organisms could be recovered from the incision and surrounding skin before, during, and after the procedure to see if they could pinpoint which would predict an SSI.
covery did not predict its development, they said. Interestingly, methicillin resistant Staphylococcus aureus and extended-spectrum β-lactamase (ESBL) producers were identified in the post-operative period in one and four different horses respectively, but none developed an SSI. “A variety of bacterial species may be isolated from equine laparotomy incisions peri-operatively without development of SSI. SSI does not appear to be solely related to bacterial contamination of the incision peri-operatively and other mechanisms—such as bacteremia— merit further investigation,” the researchers wrote. The prevalence of a positive bacterial culture increased over time even without an SSI, likely due to bacterial recolonization of the skin, they said. MeV
Lifting Large Animals Since 1957 Surgical site infection
Over a 12-month period, the researchers looked at 31 horses undergoing exploratory laparotomy at The University of Liverpool Equine Hospital because they had signs of colic. Swabs from the ventral midline of all of the horses were collected for culture and sensitivity immediately after clipping; after aseptic preparation for surgery; after closure of the linea alba; after closure of the skin, immediately after recovery from general anaesthesia; and every 48 hours post-surgery at the time of abdominal bandage changes. SSI was defined as any purulent or serous discharge from the laparotomy incision lasting more than 24 hours. They found a range of bacterial species both intraoperatively and immediately following recovery. Following aseptic preparation of the surgical site, a positive culture was obtained from only one horse. Of the 22 horses that underwent an enterotomy or anastomosis, 16 (73%) had a negative culture immediately following incisional closure. Seven horses (22.6%) developed an SSI but a positive culture from an intra-operative swab or immediately following re-
For more information: Isgren CM, Salem SE, Townsend NB, et al. Sequential bacterial sampling of the midline incision in horses undergoing exploratory laparotomy. Equine Vet J. 2018 Apr 20 (Epub ahead of print). https://onlinelibrary.wiley.com/doi/abs/10.1111/evj.12958
www.shanksvet.com • firstname.lastname@example.org ModernEquineVet.com | Issue 6/2018
New treatment strategies are rapidly gaining momentum while we continue to seek the why’s and how’s of the disease.
Photo courtesy of Dr. Teresa A. Burns
Horses with endocrine disor-
learning more about effective treatment, according to Dr. Burns, who is an associate professor of equine medicine at The Ohio State University. Both EMS and PPID share more than laminitis. They also share insulin dysregulation, appearing in 100% of horses with EMS and 30% of horses with PPID. “Nutritional therapy works well in these horses,” Dr. Burns offered, explaining that the goal is to minimize postprandial hyperinsulinemia, a recommendation based on identification of postprandial hyperinsulinemia as an independent risk factor for endocrinopathic laminitis. There are three different forms of plant carbohydrates:
ders are more prone to developing laminitis, but veterinarians still don’t know all the why’s and how’s associated with this risk. “When it comes to equine endocrine disease, two metabolic conditions—equine metabolic syndrome (EMS) and pituitary pars intermedia dysfunction (PPID)—together account for about 90% of laminitis cases and an overwhelming majority of pasture-associated laminitis,” explained Teresa A. Burns, DVM, PhD, DACVIM, at the 46th AAEP annual convention in San Antonio. Over the past 15 or so years, EMS has become prevalent in equine populations, partly due to the increase in aging horses, and veterinarians are
Issue 6/2018 | ModernEquineVet.com
1. Simple sugars, which affect postprandial hyperglycemia; 2. Starch molecules; and 3. Structural carbohydrates, which are derived from cell wall components and do not cause appreciable effects on postprandial hyperglycemia. These carbohydrates are fermented in the horse’s hindgut and represent the ideal source of calories for horses with laminitis, Dr. Burns said. KEY POINT: As a general rule, the objective is to keep dietary non structural carbohydrate (NSC) content to <10% on a dry-matter basis. This target is based largely on clinical anecdote and experience, rather than data, Dr. Burns explained, but it seems to be a safe number for horses that have severe insulin dysregulation. Fructans are a major source of carbohydrates in temperate grasses. “We’re interested in fructans be-
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Pastures with large amounts of fructans represent a risk for pasture-associated laminitis. cause they typically don’t cause large postprandial increases in blood glucose,” Dr. Burns said. “In other species, fructose has a very important influence on hepatic insulin and glucose dynamics, so it affects insulin clearance. But this isn’t something that has been described well in horses to date, particularly in the setting of EMS and PPID.” Pastures grown or cultivated under conditions in which these plants are likely to synthesize and store large amounts of fructns— what is affectionately termed football weather growth (crisp, cool, bright sun)—represent a risk for pasture-associated laminitis. Although this link is not entirely clear, it seems to involve risk to horses with EMS, so trying to minimize the amount of fructans in the
diet is likely important in managing EMS. Of note, alfalfa and legume forages in general tend not to be a lot higher in NSCs than grass forages. Even concentrate feeds formulated for horses that are carbohydrate intolerant often have more than the ideal target of <10% NSC content. “There’s value in feeding some of these concentrate feeds for vitamin and trace mineral components,” she said. “However, in horses that are severely insulin dysregulated, it might be more effective to enforce a rigorous policy of frequent small meals when using feeds with 15% to 25% or higher NSC content.”
Easier Said Than Done
“The only dietary recommendation we really need to make in the vast
At a Glance: Endocrinopathic Laminitis Two conditions account for 90% of equine laminitis • Equine metabolic syndrome (EMS) • Pituitary pars intermedia dysfunction (PPID; also known as equine Cushing’s disease) 100% of horses with EMS and 30% of horses with PPID have insulin dysregulation (ID. Hyperinsulinemia can be controlled by managing postprandial hyperglycemia. • Minimize nonstructural carbohydrate (NSC) content in the diet: keep as close as possible to 10% on a dry-matter basis. • Break diet up into small feedings: enforce a rigorous policy of frequent small meals when feeds have 15% to 25% or higher NSC content. Take Home • Restrict pasture time. • Consider early morning grazing, strip grazing, muzzle grazing. • Prior to feeding, soak forage for 30 to 60+ minutes to leach water-soluble components, such as sugars, out of hay. • Consider pharmacotherapy for short-term treatment of EMS or in refractory cases. — Levothyroxine (Thyro-L) — Metformin • In horses with PPID, initiate pergolide (Prascend) treatment as necessary
Issue 6/2018 | ModernEquineVet.com
majority of cases is to decrease the intake of rapidly fermentable carbohydrates, which also could be filed under the category of easier said than done," she said. KEY POINT: These horses benefit from diets that have much less cereal-grain-based concentrate feed than many horses are typically offered, Dr. Burns explained. Because cereal-grain-based feeds have a very high starch content— corn is almost 80% starch on a dry-matter basis for example— they should be avoided in horses with EMS, as they likely have a very profound postprandial hyperglycemic effect but also could influence the amount of weight loss achieved with dietary intervention, Dr. Burns added. Some additional suggestions include restricting or not allowing any access to pasture, particularly while a horse is actively having laminitic problems or before gaining control of the horse metabolically. The NSC content of some pastures can approach 40% on a dry-matter basis at certain times of the year, such as late November, during football weather conditions, which are ideal for storing carbohydrate (sunny, low temperatures), but this is also when most grasses are making a lot of fructans. Another important strategy that avoids high NSC content in pasture is early morning grazing. “There is a very repeatable diurnal variability in NSC content that makes sense,” Dr. Burns said. “These plants require light to synthesize sugar for metabolic processes, so when the lights go off, the plants use what they made earlier in the
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Merial is now part of Boehringer Ingelheim. ®GASTROGARD is a registered trademark of Merial. ©2018 Merial, Inc., Duluth, GA. All rights reserved. EQU-0445-EGUS0218
IMPORTANT SAFETY INFORMATION: CAUTION: Safety of GASTROGARD in pregnant or lactating mares has not been determined.
Courtesy of Dr. Teresa Burns
Caution Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Storage Conditions Store at 68°F – 77°F (20-25°C). Excursions between 59°F – 86°F (15-30°C) are permitted. Indications For treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks of age and older. Dosage Regimen For treatment of gastric ulcers, GastroGard Paste should be administered orally once-a-day for 4 weeks at the recommended dosage of 1.8 mg omeprazole/lb body weight (4 mg/kg). For the prevention of recurrence of gastric ulcers, continue treatment for at least an additional 4 weeks by administering GastroGard Paste at the recommended daily maintenance dose of 0.9 mg/lb (2 mg/kg). Directions For Use • GastroGard Paste for horses is recommended for use in horses and foals 4 weeks of age and older. The contents of one syringe will dose a 1250 lb (568 kg) horse at the rate of 1.8 mg omeprazole/lb body weight (4 mg/kg). For treatment of gastric ulcers, each weight marking on the syringe plunger will deliver sufficient omeprazole to treat 250 lb (114 kg) body weight. For prevention of recurrence of gastric ulcers, each weight marking will deliver sufficient omeprazole to dose 500 lb (227 kg) body weight. • To deliver GastroGard Paste at the treatment dose rate of 1.8 mg omeprazole/ lb body weight (4 mg/kg), set the syringe plunger to the appropriate weight marking according to the horse’s weight in pounds. • To deliver GastroGard Paste at the dose rate of 0.9 mg/lb (2 mg/kg) to prevent recurrence of ulcers, set the syringe plunger to the weight marking corresponding to half of the horse’s weight in pounds. • To set the syringe plunger, unlock the knurled ring by rotating it 1/4 turn. Slide the knurled ring along the plunger shaft so that the side nearest the barrel is at the appropriate notch. Rotate the plunger ring 1/4 turn to lock it in place and ensure it is locked. Make sure the horse’s mouth contains no feed. Remove the cover from the tip of the syringe, and insert the syringe into the horse’s mouth at the interdental space. Depress the plunger until stopped by the knurled ring. The dose should be deposited on the back of the tongue or deep into the cheek pouch. Care should be taken to ensure that the horse consumes the complete dose. Treated animals should be observed briefly after administration to ensure that part of the dose is not lost or rejected. If any of the dose is lost, redosing is recommended. • If, after dosing, the syringe is not completely empty, it may be reused on following days until emptied. Replace the cap after each use. Warning Do not use in horses intended for human consumption. Keep this and all drugs out of the reach of children. In case of ingestion, contact a physician. Physicians may contact a poison control center for advice concerning accidental ingestion. Adverse Reactions In efficacy trials, when the drug was administered at 1.8 mg omeprazole/lb (4 mg/kg) body weight daily for 28 days and 0.9 mg omeprazole/lb (2 mg/kg) body weight daily for 30 additional days, no adverse reactions were observed. Precautions The safety of GastroGard Paste has not been determined in pregnant or lactating mares. Efficacy • Dose Confirmation: GastroGard ® (omeprazole) Paste, administered to provide omeprazole at 1.8 mg/lb (4 mg/kg) daily for 28 days, effectively healed or reduced the severity of gastric ulcers in 92% of omeprazole-treated horses. In comparison, 32% of controls exhibited healed or less severe ulcers. Horses enrolled in this study were healthy animals confirmed to have gastric ulcers by gastroscopy. Subsequent daily administration of GastroGard Paste to provide omeprazole at 0.9 mg/lb (2 mg/kg) for 30 days prevented recurrence of gastric ulcers in 84% of treated horses, whereas ulcers recurred or became more severe in horses removed from omeprazole treatment. • Clinical Field Trials: GastroGard Paste administered at 1.8 mg/lb (4 mg/kg) daily for 28 days healed or reduced the severity of gastric ulcers in 99% of omeprazole-treated horses. In comparison, 32.4% of control horses had healed ulcers or ulcers which were reduced in severity. These trials included horses of various breeds and under different management conditions, and included horses in race or show training, pleasure horses, and foals as young as one month. Horses enrolled in the efficacy trials were healthy animals confirmed to have gastric ulcers by gastroscopy. In these field trials, horses readily accepted GastroGard Paste. There were no drug related adverse reactions. In the clinical trials, GastroGard Paste was used concomitantly with other therapies, which included: anthelmintics, antibiotics, non-steroidal and steroidal anti-inflammatory agents, diuretics, tranquilizers and vaccines. • Diagnostic and Management Considerations: The following clinical signs may be associated with gastric ulceration in adult horses:inappetence or decreased appetite, recurrent colic, intermittent loose stools or chronic diarrhea, poor hair coat, poor body condition, or poor performance. Clinical signs in foals may include: bruxism (grinding of teeth), excessive salivation, colic, cranial abdominal tenderness, anorexia, diarrhea, sternal recumbency or weakness. A more accurate diagnosis of gastric ulceration in horses and foals may be made if ulcers are visualized directly by endoscopic examination of the gastric mucosa Gastric ulcers may recur in horses if therapy to prevent recurrence is not administered after the initial treatment is completed. Use GastroGard Paste at 0.9 mg omeprazole/lb body weight (2 mg/kg) for control of gastric ulcers following treatment. The safety of administration of GastroGard Paste for longer than 91 days has not been determined. Maximal acid suppression occurs after three to five days of treatment with omeprazole. Safety • GastroGard Paste was well tolerated in the following controlled efficacy and safety studies. • In field trials involving 139 horses, including foals as young as one month of age, no adverse reactions attributable to omeprazole treatment were noted. • In a placebo controlled adult horse safety study, horses received 20 mg/kg/ day omeprazole (5x the recommended dose) for 90 days. No treatment related adverse effects were observed. • In a placebo controlled tolerance study, adult horses were treated with GastroGard Paste at a dosage of 40 mg/kg/day (10x the recommended dose) for 21 days. No treatment related adverse effects were observed. • A placebo controlled foal safety study evaluated the safety of omeprazole at doses of 4, 12 or 20 mg/kg (1, 3 or 5x) once daily for 91 days. Foals ranged in age from 66 to 110 days at study initiation. Gamma glutamyltransferase (GGT) levels were significantly elevated in horses treated at exaggerated doses of 20 mg/kg (5x the recommended dose). Mean stomach to body weight ratio was higher for foals in the 3x and 5x groups than for controls; however, no abnormalities of the stomach were evident on histological examination. Reproductive Safety In a male reproductive safety study, 10 stallions received GastroGard Paste at 12 mg/kg/day (3x the recommended dose) for 70 days. No treatment related adverse effects on semen quality or breeding behavior were observed. A safety study in breeding mares has not been conducted. For More Information Please call 1-888-637-4251 Marketed by: Merial, Inc., Duluth, GA 30096-4640, U.S.A. Made in Brazil ®GastroGard is a registered trademark of Merial, Inc. ©2016 Merial, Inc. All rights reserved. Rev. 05-2011
These are all EMS patients with classic conformation associated with equine metabolic syndrome.
day. The nadir in NSC content for most pasture forages will be in the very early morning. Likewise, strip grazing is an alternative strategy and a grazing muzzle is another great idea.” Other approaches are based on offering a grass hay that has low NSC content on testing, ideally 10% to 12%, and objectively based on proximate analysis—sometimes repeated proximate analyses—depending on how frequently clients purchase hay. As a strategy that leaches soluble carbohydrates out of hay, soaking actually is effective, but it’s certainly not a panacea, Dr. Burns said. “For these horses, we recommend feeding low NSC forage at 1% to 2% of their ideal body weight per day and monitoring them over time to make sure progress is being made. If after 4 to 8 weeks they are not making progress, that’s probably when you need to dial it down a bit,” she explained. Dr. Burns recommended soaking forage for 30 to 60 minutes (sometimes longer) prior to feeding so water-soluble components, such as simple sugars, are decreased in the hay as fed. “Does it work? Yes, it does,” she stressed. In fact, several studies have shown that soaking hay very effectively leaches sugars and water-soluble components. In one study, an average of 27% of the decrement of NSC content in grass forages was leached into the soaking fluid. Protein fraction was not affected by soaking, but other components—most notably electrolytes (notably, sodium)— will be leached out of hay. 8
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The bottom line is that soaking lowers NSC content, but the starting point also matters. “If you start with hay that has an excessively high NSC content, a loss of 25% might not render that forage sufficiently safe to feed to a horse with ID. That’s when the proximate analysis becomes helpful,” Dr. Burns emphasized.
“If nutrition fails and you’re absolutely sure your recommendations are being followed religiously, it‘s time to consider pharmacotherapy,” Dr. Burns said. Metformin is the most commonly prescribed drug in the United States for treating human diabetes. Much less is known about using it in horses , but the goals seem to be: • Increase insulin sensitivity • Mitigate hyperinsulinemia • Encourage weight loss KEY POINT: Some recommend using pharmacotherapy for short-term treatment when management changes are in flux or in refractory cases of EMS, especially when tight dietary control does not help the horse lose weight. Levothyroxine (Thyro-L, Vet-A-Mix) has been used to treat horses with ID for a long time—even before veterinarians were consciously treating horses with ID. “This drug was given to a lot of horses to treat hypothyroidism, when in actuality those horses likely had manifestations of EMS. With administration of thyroid hormones, predictably good things happen to horses
Courtesy of Dr. Teresa Burns
These are all EMS patients with classic conformation associated with equine metabolic syndrome.
with ID. Adipose tissue lipolysis is enhanced; in addition, these hormones are calorigenic and thus broadly increase the horse’s metabolic rate. That’s all good stuff,” she explained. Remember that there is no known node of intermediary metabolism that is untouched by thyroid hormones, so this needs to be used just as a tool to achieve a desired effect, then likely taken away. “In studies of longer-term use of thyroid hormones, there was no significant evidence that they are unsafe, but horses haven’t been receiving hormone drugs for years and years, so at the moment, we recommend this treatment only if the horse is not responding to nutritional therapy and exercise or can’t exercise because of intractable foot pain,” Dr. Burns said, adding that a dose of 0.1 mg/kg once a day likely renders the horse hyperthyroid. This is rarely associated with clinical signs of hyperthyroidism, although there have been a couple of cases seen at The OSU clinic. KEY POINT: Restrict access to forage when giving levothyroxine because it can cause compensatory hyperphagia. Again, Dr. Burns emphasized, this temporary tool should be used
The role of metformin, prescribed often for diabetics, remains unclear in horses. to accelerate weight loss. “At OSU, we use it for about 3 to 6 months and then taper it off over 2 to 4 weeks following cessation of therapy. Another product that is frequently used is biguanides, which Dr. Burns called an interesting class of drugs for which the mechanism of action is not definitively known, but one effect is activation of an enzyme called AMPK [5’AMP activated protein kinase]. AMPK agonism is probably very beneficial in multiple species with metabolic problems. Metformin has been used extensively in people and its use in horses has been increasing over the past several years. Metformin administration causes a broad global activation of AMPK, which has some effect on all except a few tissues, at least in theory. “That
isn’t known with certainty in horses,” Dr. Burns explained, “but it is well characterized in people and in rodents. You might see glycolysis, increased beta-oxidation and increased insulin sensitivity—all of which can represent actual improvement in insulin dysregulation when activation of AMPK is stimulated. Metabolically, this is good and why metformin has been successful in people.” In horses, she continued, metformin was used more often before its affects were fully known. Initially, doses were extrapolated from human use—usually 10 to 15 mg/kg twice a day, but now there are some clinical data. Initially, a large study from 2008 looked at metformin in clinical cases. The broad takeaway: the drug appeared to be safe, and horses and ponies seemed to get better while receiving it. Of note: these patients also received nutritional intervention and exercise. But then a second study found the oral bioavailability of metformin in horses to be 4% to 7%, and metformin use dropped significantly because horses were not absorbing it well. KEY POINT: Since then, there has been a bit of a re-evaluation of metformin. A more recent report suggested that metformin, even if it is not absorbed from the GI tract,
might act locally in the GI tract to prevent absorption of NSC components in the diet, so it mitigates postprandial hyperglycemia in animals that receive it and then are given a carbohydrate challenge. “Even if it doesn’t do anything other than this, it might be strategically useful in a patient with EMS that you want to reintroduce to pasture,” she said. “This might be the horse’s pasture pill, if you will, and might be an interesting use of metformin that needs to be validated in the future.” At this time, she and her colleagues at OSU are recommending 15 to 30 mg/kg orally twice a day for patients with refractory ID. In addition to metformin, a variety of supplements and nutraceuticals (eg, chromium, magnesium, cinnamon) have been proposed to manage EMS in some species, but there is no objective evidence supporting the recommendation of most of these products, so Dr. Burns is waiting for more data before making a solid recommendation. KEY POINT: In 2011, Prascend (Boehringer Ingelheim Vetmedica) became fully FDA licensed for the treatment of PPID in horses. Treatment for most light-breed horses is initiated at 1 mg per horse per day; administration of half of this
dose for 10–14 days before increasing to 1 mg may help mitigate inappetence associated with the treatment. Some studies have looked at pergolide from an efficacy standpoint, Dr. Burns pointed out. One looked at what happens when pergolide is administered to normal horses for 6 months. Interestingly, the adrenocorticotropic hormone (ACTH) concentration, which was effectively suppressed even in these normal horses, started to climb quickly when the drug was discontinued. With a half-life of 18 to 24 hours, ACTH blood concentration increased significantly within five days after the dose was stopped. Notably, Dr. Burns said, 43% of horse owners treating a horse with PPID reported improvement after two months and 50% of horses were alive almost five years after diagnosis. In addition, 95% of horse owners said they would do the regimen again, so it seems this is an effective treatment for PPID that is well-received by horse owners,” Dr. Burns concluded.
The Future Holds Promise
A couple of years ago, researchers from The OSU College of Veterinary Medicine announced the Vision 2020 effort of the veterinary
community to conquer laminitis by 2020. Researchers from around the world have been making progress in uncovering the pathways that lead to laminitis, including many international collaborative efforts. Likewise, researchers from the University of California, Davis, Center for Equine Health Studies has investigated the underlying cellular changes that precede laminitis, with the goal of developing better diagnostics, preventive and therapeutic options. Other laminitis research funded by the Animal Health Foundation (AHF) has looked at ways to deliver medication directly to the foot and the inner workings of insulin regulation in the GI tract. In addition, state-of-the-art gene analysis conducted by Samantha Brooks, PhD, at the University of Florida Brooks Equine Genetics Laboratory measured chemical signatures and discovered landmark genetic markers. When it comes to endocrinopathic laminitis, researchers are making exciting strides in uncovering the why’s and how’s of the disease, and today’s treatment strategies continue to be encouraging, so much so, Dr. Burns said, “that we’re getting closer to preventing or stopping its progress as hoped by 2020.” MeV
For more information: Davis JL, Kirk LM, Davidson GS, et al. Effects of compounding and storage conditions on stability of pergolide mesylate. J Am Vet Med Assoc. 2009;234(3):385-389. https://www.dovepress.com/equine-pituitary-pars-intermedia-dysfunction-current-perspectives-on-d-peerreviewed-fulltext-article-VMRR Durham AE, Rendle DI, Newton JE. The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine Vet J. 2008;40(5):493-450. https://onlinelibrary.wiley.com/doi/abs/10.2746/042516408X273648 Hustace JL, Firshman AM, Mata JE. Pharmacokinetics and bioavailability of metformin in horses. Am J Vet Res. 2009;70(5):665-668. Longland AC, Barfoot C, Harris PA. Effects of soaking on the water-soluble carbohydrate and crude protein content of hay. Vet Rec. 2011;168(23):618. https://veterinaryrecord.bmj.com/content/168/23/618.long McFarlane D, Bonse H, Knych HK, et al. Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction. J Vet Pharmacol Ther. 2017;40(2):158-164. https://onlinelibrary.wiley. com/doi/abs/10.1111/jvp.12339 Rendle DI, Rutledge F, Hughes KJ, et al. Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Equine Vet J. 2013;45(6):751-754. https://onlinelibrary.wiley.com/doi/abs/10.1111/evj.12068 10
Issue 6/2018 | ModernEquineVet.com
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Helps Heal Distal Limb Wounds B
is left to heal by second intention, according to Dr. Tsang. “Honey has been shown to have strong antibacterial activity due to a combination of low pH, high osmolarity and the production of low levels of hydrogen peroxide from the enzyme glucose oxidase,” Dr. Tsang said here at the 63rd Annual AVMA Convention in San Antonio, Texas. “It has also been shown to have anti-inflammatory and antioxidant activity. The majority of bioactive chemicals within honey have still not been identified.” In animal models and in some human clinical trials, honey has been shown to reduce pain, deodorize wounds, reduce infection rates, facilitate debridement of necrotic tissue, promote granulation tissue formation and reduce scarring. Manuka honey is a monofloral honey produced by bees that forage on the Manuka tree in southeastern Aus-
Images courtesy of Dr. Albert S. H. Tsang.
the role of honey in wound care, the bee by-product is often relegated to an afterthought. A dearth of clinical studies, an increasing number of varietals and a general lack of experience may keep clinicians away from this potentially viable topical application. Albert S. H. Tsang, BVSc (Hons), University Veterinary Teaching Hospital Camden, New South Wales, Australia, and colleagues recently evaluated the effects of Manuka medical grade honey on the treatment of equine distal limb wounds. Frequently, wounds of the distal limb are complicated by gross contamination, and excessive skin tension and tissue evulsion can preclude primary closure. The wound
The wound before and after seven days of treatment with Manuka honey.
Issue 6/2018 | ModernEquineVet.com
MARQUIS® (15% w/w ponazuril) Antiprotozoal Oral Paste by Merial
you have to face head-on. Equine Protozoal Myeloencephalitis (EPM) is an expert in deception and may at first be confused with other issues, such as lameness. Stopping the parasite responsible for EPM will stop further damage to the horse’s brain and CNS. Time matters. The sooner EPM is detected and diagnosed, the better. That’s why you need a tube of Marquis® (15% w/w ponazuril) readily available to initiate treatment immediately. MARQUIS is a powerful and fast-acting antiprotoxozl.
The signs can be subtle. The treatment should be aggressive.
MARQUIS Freedom of Information Summary and Supplement and product label.
IMPORTANT SAFETY INFORMATION: The safe use of MARQUIS in horses used for breeding purposes, during pregnancy, or in lactating mares, has not been evaluated. In animal safety studies, loose feces, sporadic inappetence, lost weight, and moderate edema in the uterine epithelium were observed. Merial is now part of Boehringer Ingelheim. ‰MARQUIS is a registered trademark of Merial. ©2018 Merial, Inc., Duluth, GA. All rights reserved. EQU-0462-MARQ0218
MARQUIS® (15% w/w ponazuril) Antiprotozoal Oral Paste Caution: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.
Images courtesy of Dr. Albert S. H. Tsang
For The Treatment Of Equine Protozoal Myeloencephalitis (EPM) In Horses For Oral Use Only BRIEF SUMMARY Before using MARQUIS, please consult the product insert, a summary of which follows: INDICATIONS MARQUIS (ponazuril) is indicated for the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. WARNINGS For use in animals only. Not for use in horses intended for food. Not for human use. Keep out of reach of children. PRECAUTIONS Prior to treatment, a complete neurologic exam should be completed by a veterinarian. In most instances, ataxia due to EPM is asymmetrical and affects the hind limbs. Clinicians should recognize that clearance of the parasite by ponazuril may not completely resolve the clinical signs attributed to the natural progression of the disease. The prognosis for animals treated for EPM may be dependent upon the severity of disease and the duration of the infection prior to treatment. The safe use of MARQUIS (ponazuril) in horses used for breeding purposes, during pregnancy, or in lactating mares, has not been evaluated. The safety of MARQUIS (ponazuril) with concomitant therapies in horses has not been evaluated. ADVERSE REACTIONS In the field study, eight animals were noted to have unusual daily observations. Two horses exhibited blisters on the nose and mouth, three animals showed skin reactions for up to 18 days, one animal had loose stools, one had a mild colic on one day and one animal had a seizure while on medication. The association of these reactions to treatment was not established. ANIMAL SAFETY SUMMARY MARQUIS (ponazuril) was administered to 24 adult horses (12 males and 12 females) in a target animal safety study. Three groups of 8 horses each received 0, 10 or 30 mg/kg (water as control, 2X and 6X for a 5 mg/kg [2.27 mg/lb] dose). Horses were dosed after feeding. One half of each group was treated for 28 days and the other half for 56 days followed by necropsy upon termination of treatment. There were several instances of loose feces in all animals in the study irrespective of treatment, sporadic inappetence and one horse at 10 mg/kg (2X) lost weight while on test. Loose feces were treatment related. Histopathological findings included moderate edema in the uterine epithelium of three of the four females in the 6X group (two treated for 28 days and one for 56 days). For customer care or to obtain product information, including a Material Safety Data Sheet, call 1-888-6374251 Option 2, then press 1. ®MARQUIS is a registered trademark of Merial. ©2016 Merial, Inc., Duluth, GA. All rights reserved.
The wound before and after seven days of treatment with Manuka honey.
tralia and New Zealand. This varietal is known for its superior antibacterial properties against multidrug resistant bacteria. The properties are derived from the production of methylglyoxal, not hydrogen peroxide. Methylglyoxal is a chemical approximated from the Manuka tree. Unique Manuka factor (UMF) is a standardized grading system for the honey varietal. A jar of Manuka honey that is labeled UMF20 has the equivalent antibacterial activity of a 20% solution of phenol. The higher the UMF, the more efficacious the honey, he explained. “From previous studies in an equine distal limb wound-healing model, our group has found that UMF20 Manuka honey reduces the retraction phase of healing, increases the rate of healing of full thickness skin wounds, increases the rate of angiogenesis, and improves the quality of fibroplasia,” Dr. Tsang said. For this study, the researchers hypothesized that UMF20 Manuka honey would improve wound-healing characteristics when compared with generic multifloral honey purchased from a supermarket, and saline controls. In addition, they believed that UMF20 and UMF5 Manuka honey would improve the earliest phases of wound healing with minimal contamination. As UMF20 gains popularity, the price
has also increased drastically. This led the team to compare UMF20 Manuka honey with UMF5 Manuka honey. Two full thickness skin wounds measuring 2.5 cm × 2.5 cm were created on the dorsomedial aspects of the hind limbs bilaterally in eight Standardbred horses. The wounds were not created under aseptic conditions, but they were not contaminated with feces as they had been in previous models. “The model used in this study had minimal contamination compared with previous models which involved contaminating the wounds with feces for 24 hours,” Dr. Tsang said. “We wanted to negate the requirement for antibacterial activity from the Manuka honey to determine whether its ability to modulate the immune system was the primary way Manuka honey improved healing.” The horses were randomized to one of four treatments: UMF20 Manuka honey, UMF5 Manuka honey, generic storebought honey or saline. The wounds were treated and bandaged daily for 12 days. On day 13, the bandages were removed, and the wounds were left to heal by second intention. On day 21, wounds treated with UMF20 honey were smaller when compared with the wounds treated with UMF5. Overall,
For more information: Tsang AS, Dart AJ, Sole-Guitart A, et al. Comparison of the effects of topical application of UMF20 and UMF5 Manuka honey with a generic multifloral honey on wound healing variables in an uncontaminated surgical equine distal limb wound model. Aust Vet J. 2017 Sep;95(9):333-337. doi: 10.1111/avj.12616. Epub 2017 Jul 17 https://onlinelibrary.wiley.com/doi/abs/10.1111/avj.12616 14
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wounds treated with UMF20 Manuka honey healed faster than the controls (P=0.01) and the wounds treated with store-bought honey (P=0.02). No statistical difference was noted for overall healing rate among the groups. “It was interesting that there did not appear to be an effective treatment with generic multifloral honey on wound healing,” he explained. “This may be because commercial food-grade honey bought from the supermarket undergoes heat pasteurization, which can actually de-
stroy the enzyme glucose oxidase. It is also possible that the high temperatures of pasteurization could also inactivate other biochemical bioactive compounds within the generic honey.” One of the limitations of the study was the use of hind limbs instead of forelimbs. While the healing patterns are similar, hind limb wounds typically take longer to heal than those of the forelimbs. Dr. Tsang noted that caution should be used when comparing this study with other studies that involved forelimbs.
“In terms of further research, isolation of the bioactive compounds within Manuka honey that are involved in the immune modulatory effects should be targeted, as well as whether the concentration of these compounds actually is correlated to the UMF factor or its antibacterial activity,” Dr. Tsang said. “It would also be prudent to determine whether generic multifloral honey that is not heat-treated—but rather sterilized with gamma irradiation— would have beneficial effects on wound healing.” MeV
Is Intense Exercise Fatal to Racehorses? The mortality rate and risk were lowest for Standardbreds, at 0.28 deaths per 1,000 race starts, and an annual death rate of 0.23% to 0.24%. This breed is given more extensive training preparation and racing, he said. Mortality related to high-intensity exercise in Quarter Horse was 1.49 deaths per 1,000 race starts, with an annual death rate of 0.60% to 0.69% from the activity. For all breeds, musculoskeletal injury was the major contributing cause of mortality. The study revealed that the gender of Standardbreds strongly affects mortality risk, with young stallions at higher risk than mares or geldings. Among older horses, geldings have a higher risk than males. Thoroughbred stallions face a higher risk than Standardbred stallions. Training strategies could be modified to address animal welfare, Dr. Physick-Sheard said. “We’re starting to focus more on the things that are potentially inherent to the breeds of horse, as opposed to characteristics of the work they perform,” he said. “As we get more insight into those horse factors, we become more aware of other influences that are possible causes of increased mortality risk.” MeV Credit: © Lukas Gojda / Fotolia
Intense racing can be fatal to racehorses, according to Peter Physick-Sheard BVSc, MSc, FRCVS, associate professor at the University of Guelph (Ontario), Veterinary College. Dr. Peter Physick-Sheard and his colleagues examined 1,713 racehorse deaths from 2003 to 2015 to compare mortality in three racing breeds. With the support of Ontario’s Alcohol and Gaming Commission, researchers analyzed race and trial run data from Ontario horse racing. A provincial registry of equine mortality requires mandatory reporting of all deaths occurring within 60 days of a race or trial run. Most racing in North America involves intense exertion over a relatively short distance. The researchers wanted to characterize and quantify exercise-associated mortality in racehorses and identify breed differences. “The study reveals parallels between mortality and the intensity of the overall management of the horses, their lifestyle and the type of work they do,” said Dr. Physick-Sheard, of the Department of Population Medicine. “Training and racing at top speed within a short time and space is a health risk for horses.” Dr. Physick-Sheard discovered that Thoroughbreds had the highest exercise-associated mortality rate and risk. Out of every 1,000 races, 2.27 deaths were exercise-associated. About 1% of racing Thoroughbreds die annually in association with racing or trial runs.
New research finds a link between racing at top speed for a short time and increased mortality risk.
For more information: Physick-Sheard PW, Avison A, Chappell E, et al. Ontario Racehorse Death Registry, 2003–2015: Descriptive analysis and rates of mortality. Equine Vet J. 2018 Apr 19 (Epub ahead of print) DOI: 10.1111/evj.12955. https://onlinelibrary.wiley.com/doi/abs/10.1111/evj.12955 ModernEquineVet.com | Issue 6/2018
Stallion With Suspected Tetanus By Deanna Biondo-Bell, RVT, BS On Dec. 6, 2014, a 5-year-old Arabian stallion weighing 433.6 kg presented at the University of Missouri’s Veterinary Health Center (VHC) with suspected tetanus. The week of Nov. 24, 2014, the client noticed the stallion incurred a traumatic hoof injury to the right front hoof. The owner soaked the foot with Epsom salt and betadine for 10 minutes BID for several days. The stallion was then turned back out into his pen. On Dec. 4, 2014, the owner noticed the third eye lid protruding and the horse was walking favoring his right front leg. The referring veterinarian was called on Dec. 6, 2014 due to more pronounced symptoms and food dribbling out of the stallion’s mouth. The referring veterinarian checked the foot wound and the stallion’s mouth and referred it to the VHC. The history obtained at admission revealed the stallion did not have a current EIA (Coggins), was not up to date on vaccinations and specifically had never been vaccinated with tetanus toxoid. He had not received any dental or farrier care and was not broke to ride. When entering the clinic, the stallion was anxious and hyper-responsive. He staggered getting off of the trailer, walked with a stiff gait and all of his muscles were rigid. A physical exam was performed by the attending clinician, house officer and student. The physical exam results revealed a normal rectal temperature of 98.9 ° F. The heart rate was elevated at 56 beats/min, and in normal sinus rhythm. The respiratory rate was elevated at 80 breaths/min and breaths were shallow. Normal borborygmi were auscultated in all four quadrants. Initial blood work submitted was a complete blood count, chemistry panel and packed cell volume. The stallion’s PCV was 38% and considered to be mildly hemoconcentrated and slightly dehydrated. The segmented neutrophils were elevated at 11.64 (2.26–8.85) and white blood cells were within normal range at 13.86 (5.4–14.3). MCHE was slightly elevated at 39.6 g/dL (31–38.6) as was fibrinogen at 0.5 gm/dL (0.1–0.4). The chemistry panel showed an elevated glucose of 133 mg/dL (83–113) which was most likely caused by stress. The creatinine kinase (CK) was significantly elevated at 1,476 U/L (109–456) due to muscle damage. Following the physical exam, the stallion was sedated with Dormosedan to facilitate placement of an Angiocath 14-ga fluorinated ethylene propylene polymer 16
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intravenous catheter in the left jugular vein. A presumed diagnosis of tetanus was made based on the history (lack of vaccination), wound and clinical signs—which were consistent with tetanus. Treatment options were discussed with the owner. The owner elected to proceed with general anesthesia to administer tetanus antitoxin into the intrathecal space and to thoroughly clean the hoof wound. A discussion took place between the anesthesiologist and attending clinician regarding the best injectable anesthesia protocol for this stallion’s situation and determined that in this case, ketamine should not be used due to potential risk of seizure and increase in muscle rigidity. The decision was made to induce and maintain anesthesia using propofol to ensure the best outcome. At 6:55 pm, IV xylazine was administered as a preanesthetic drug. Five minutes later, anesthesia was induced with the administration of 5% guaifenesin, which was given to effect, followed by IV propofol. The stallion responded well and induction was without incident. He was intubated with a size 22 endotracheal tube and placed on an oxygen-demand valve. Fifteen minutes later, an additional dose of IV propofol was administered to maintain anesthesia. The patient was placed in left lateral recumbency and the atlanto-occipital joint was prepared in sterile fashion. The attending clinician aspirated 30 mL of cerebral spinal fluid. Six mL of cerebral spinal fluid was sent to the on-site diagnostic lab for analysis. We administered 9,000 units of intrathecal tentanus antitoxin and 7,500 IV units. The right front hoof was thoroughly cleaned, packed with metronidazole and bandaged. The total anesthesia time was 25 minutes and the stallion’s recovery was uneventful. He was moved to a dark stall at the back of the hospital in hopes to keep noise and stimulus to a minimum. The stallion was monitored closely to make sure he was able to eat and drink and that his symptoms were not worsening. He was also carefully monitored for anaphylaxis and the potential for the rare reaction to tetanus antitoxin known as Theiler’s Disease Associated Virus. Theiler’s Disease Associated Virus is a virus that causes acute hepatic necrosis. Clinical signs include lethargy, anorexia, icterus, photosensitization, diarrhea, clotting deficiencies, or neurologic signs from hepatic encephalopathy or hypoglycemia. Most commonly, these signs will show up 4 to 10 weeks after the antitoxin is given. The stallion’s treatment protocol was as follows: IV flunixin meglumine BID for pain and inflammation, and IV penicillin G potassium QID to combat the in-
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The treatment of tetanus requires a multimodal approach. The infection that initiated the disease must be directly addressed with wound cleaning and antimicrobial therapy. Unbound toxin must be addressed to prevent worsening of the condition and this is done through the administration of tetanus antitoxin. Tetanus antitoxin can be given intravenously, subcutaneously or into the intrathecal space directly. Intrathecal administration of antitoxin is a more direct route of targeting the toxin that has entered the central nervous system. This administration is done under general anesthesia requiring the patient to recover, which can be a risk. In this particular case, we elected the intrathecal route in hopes of blocking any further binding of the toxin in the CNS. I was the technician on call when the stallion arrived for emergency treatment and helped with treatments throughout his stay in the hospital. I found this case interesting because I had not participated in the treatment of a tetanus case. These cases generally have a poor prognosis, are difficult to treat and expensive. It was encouraging to see the stallion’s symptoms improve while in the clinic and ultimately discharged back to the care of his owner. Some challenges faced in this case were adhering to a strict budget and safely treating a 5-year-old stallion with little to no training without causing him more stress. This case was also successful in part to the willingness of the client to treat, the team of students participating in his daily care, the team of veterinary technicians, and, of course, the amazing work of the attending clinician, residents, anesthesiologist and interns.
fection. To insure hydration, Lactated Ringer’s Solution was administered. To help keep the stallion relaxed and quiet during his first morning in the clinic he was given IV detomidine. During his first full day in the clinic his respiration (88 breaths/min) and heart rate (52 beats/ min) were elevated and he had a normal rectal temperature. He was standing and able to eat and drink. The stallion was fed Equine Senior mash, mixed grass hay and water ad lib. He was able to defecate and urinate without complication. He was hypersensitive to noise stimulus and his gait was stiff and ridged, and his muscles remained firm when palpated. On the second day in the clinic the stallion received 4,500 units of subcutaneous tetanus antitoxin in both the right and left side of his neck for a total of 9,000 units. It was recommend to follow a three-day protocol of administering tetanus antitoxin after initial treatment. The cerebrospinal fluid cytology results were posted. No cytologic abnormalities were seen and micro protein was 49 mg/dl. The stallions PCV was 37% and total protein was 6.5 mg/dl. He continued on IV fluids and the penicillin G potassium was increased. His condition was stable and he continued to urinated, defecate, consume feed and water without complication. An attempt was made to change his hoof bandage but it was unsuccessful due to his stiff muscles and lack of training. He was continued on penicillin G potassium due to budget concerns. He required two doses of detomidine due to agita18
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tion. The stallion was placed on a guaifenesin to address the agitation and muscle stiffness. The other options were methacarbamol, which would be cost prohibitive in this case, or acepromazine, which is not recommended for use in stallions. Cotton was placed in his ears and barricades placed around his stall to decrease traffic and noise. On day three, the stallion received a second dose of tetanus antitoxin subcutaneously. IV fluids were discontinued in the morning but due to his PCV of 45%, he was given an IV fluid bolus in the late afternoon. His symptoms continued to improve, and he walked with a smoother gait. The stallion became more aware of his surroundings and greeted people at the door—eager for his food. The right front hoof bandage was successfully changed. The final dose of tetanus antitoxin was administered subcutaneously on the fourth day. The stallion’s symptoms improved each day. The stiffness in his limbs lessened, muscle rigidity decreased and he was able to start resting a hind foot and gained some tail mobility. He sustained himself without the assistance of fluid therapy. His respiratory rate remained elevated (64 breaths/min) but his heart rate normalized as did his rectal temperature. The afternoon dose of flunixin meglumine was decreased. For the next eight days until discharge the stallion continued to show mild improvement. Unfortunately, the better he felt, the worse his behavior became mak-
ing it difficult to treat him safely. After day five it was no longer safe to take a rectal temperature and every treatment required two people when entering his stall. Penicillin G potassium was discontinued after seven days and he was switched to oral flunixin meglumine paste being fed over his grain on the seventh day. His heart rate and respiratory rate remained elevated the entire stay—most likely caused by stress. The stallion was discharged on Dec. 19. He was sedated for the trailer ride to reduce travel stress. This was only his second time on a trailer and the first was arriving at the clinic. He was sent with the following home care recommendations: Provide a comfortable, low stress environment. It would take weeks for the horse to metabolize the bound tetanus neurotoxin and to normalize. Provide a well-bedded quiet, and dark stall for the next few weeks (this is especially important because he is a stallion). Free choice hay and water should be made available. He should be kept away from mares, other stallions, and any other distractions as stimulation could worsen his symptoms. It was strongly recommended he receive a booster in 30 days of tetanus toxoid from his regular veterinarian, then yearly vaccinations after that. The right-front-hoof bandage should be changed weekly and he should also receive regular farrier work after returning to normal to prevent quarter chipping and the possibility of re-infection. The owner was instructed to notify a veterinarian immediately if the stallion became recumbent, developed a rectal temperature greater than 101.5° F,
showed signs of colic, exhibited difficulty breathing or increased reparation rate, become agitated or hyperactive, or displayed any charges in his ability to eat, drink, urinate or defecate. Horses are supremely sensitive to tetanus and are the second-most susceptible species, second only to humans. Colostridium tetani spores are ubiquitous in soil and enter the body through open wounds. This anaerobic bacteria produce virulent toxins that travel to the central nervous system, attacking muscle-controlling nerves. In this particular case the bacteria entered through a small wound in the hoof. Horses with tetanus often present with the classic clinical signs, which include flared nostrils, the “sardonic grin,” a stiff stance, sweating, prolapsing of the third eyelid, muscle spasms, a raised tail head and difficulty eating due to lockjaw and the “saw horse stance.” This disease has often progressed to the point that treatment is unrewarding when we first see the animal. Treatment is expensive and the animals typically require long-term supportive care and hospitalization. MeV
About the author
Deanna Biondo Bell, RVT, BS, is a senior veterinary technician in the equine and radiology sections at the University of Missouri Veterinary Teaching Hospital. In addition to using her skills in radiology, she continues to work in her area of strength by teaching 3rd and 4th year veterinary students equine radiology.
New Video Series by Dr. Sue Dyson One of the UK’s most eminent equine orthopedic specialists, Sue Dyson, MA, Vet MB, PhD, DEO, FRCVS, is playing a leading role in a series of new educational videos aimed at helping riders, owners, trainers and veterinarians to recognize musculoskeletal pain and subtle lameness sooner. Dr Dyson, who is the head of Clinical Orthopaedics at the Centre for Equine Studies at the Animal Health Trust in Newmarket, UK, said that the videos are a valuable learning tool to help improve the welfare and performance of the ridden horse. The video series give the viewer clear, practical guidance on how to pinpoint the notoriously elusive common culprit for poor performance and behavioral issues—pain. VIDEO 1 explains the familiar indicators of lameness before revealing pain’s less obvious signs such as facial expressions and behavior
VIDEO 2 outlines a protocol for establishing the main sources of underlying pain associated with subtle or obvious lameness in horses
VIDEO 3 shows how to recognize the facial expressions of a horse in pain
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