Practitioner Issue 4, 2018

Published by the Florida Association of Equine Practitioners, an Equine-Exclusive Division of the Florida Veterinary Medical Association Issue 4 • 2018

PRACTICAL EQUINE REHABILITATION FOR THE PRACTITIONER

TRACY A. TURNER DVM, MS, DACVS, DACVSMR

NAVICULAR BURSA

LAURA M. RIGGS DVM, Ph.D., DACVS-LA, DACVSMR BRITTA LEISE DVM, Ph.D., DACVS-LA

CLINICAL APPLICATIONS OF LAMINITIS RESEARCH LAURA M. RIGGS DVM, Ph.D., DACVS-LA, DACVSMR BRITTA LEISE DVM, Ph.D., DACVS-LA

THERAPEUTICS FOR INFECTIOUS ENDOMETRITIS: A CLINICAL PERSPECTIVE

RYAN A. FERRIS DVM, MS, DACT

56

th

ANNUAL OCALA

EQUINE CONFERENCE FEBRUARY 1-3, 2019 | OCALA, FLORIDA

The President's Line EXECUTIVE COUNCIL COREY MILLER

DVM, MS, DACT FAEP COUNCIL PAST PRESIDENT

cmiller@emcocala.com

ANNE L. MORETTA VMD, MS, CVSMT

maroche1@aol.com

JACQUELINE S. SHELLOW DVM, MS REPRESENTATIVE TO FVMA EXECUTIVE BOARD

jackie@shellow.com

ARMON BLAIR DVM

abeqdoc@aol.com

ADAM CAYOT DVM

adamcayot@hotmail.com

AMANDA M. HOUSE DVM, DACVIM

Dear Fellow Equine Practitioners, With another year coming to a close, this will be my last missive for The Practitioner. After a three-year tenure, this weary traveler is being succeeded by Dr. Armon Blair in 2019.We are excited to welcome a new face as the FAEP Council President.

This past year has been very productive with successful conferences in both Ocala and Naples, Florida. We also hosted the UF Student Appreciation Day held in Ocala, Florida at prominent equine practices throughout, and the program was supported by industry partners. The day provided veterinary students with valuable hands-on experiences in various areas commonly seen within equine practice. As in years past, this was a very popular and highly successful event. The 2018 Promoting Excellence Symposium (PES) was another highlight of the CE season with attendees from across North America making this a great venue to exchange ideas, make new friendships and enjoy a beautiful facility.

The 2019 CE season is almost upon us with the 56th Annual Ocala Equine Conference starting the year off from February 1-3, 2019.

We have another full and exciting program to offer, including the ever-popular Comprehensive Equine Ultrasound Wet Lab on the Friday before the conference begins. Save the date for the 2019 Promoting Excellence Symposium being held October 10-13, 2019 at the beautiful Sanibel Harbour Marriott Resort & Spa in Ft. Myers, Florida.

As always, the FAEP Council would not be able to provide you with the quality educational programs we do without our educational partners — we offer our sincere appreciation for their continued support. In addition, the FAEP prides itself on offering attendees first-class education in a more intimate setting, allowing more contact with speakers than what is offered at any other CE event.

I look forward to welcoming Dr. Blair to the position of FAEP Council President in 2019. I hope everyone had a wonderful holiday season, and I look forward to seeing you all in this New Year.

housea@ufl.edu

Ruth-Anne Richter, BSc (Hon), DVM, MS FAEP Council President PHILIP J. HINKLE EXECUTIVE DIRECTOR

phinkle@fvma.org

Opinions and statements expressed in The Practitioner reflect the views of the contributors and do not represent the official policy of the Florida Association of Equine Practitioners or the Florida Veterinary Medical Association, unless so stated.

Placement of an advertisement does not represent the FAEP’s or FVMA’s endorsement of the product or service.

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2 The Practitioner

Issue 4 • 2018

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PRACTICAL EQUINE REHABILITATION FOR THE PRACTITIONER TRACY A. TURNER | DVM, MS, DACVS, DACVSMR INTRODUCTION Human physical therapy describes the care and services provided by or under the direction of a licensed physical therapist. In human medicine, physical therapists are regarded as clinicians. They engage in an examination process that includes taking the patient/ client history, conducting a systems review, and performing tests and measures to identify potential and existing problems. Based on their judgments, physical therapists provide interventions, conduct re-examinations, and modify interventions as necessary to achieve anticipated goals and expected outcomes. They are the only professionals who provide physical therapy examinations, evaluations, diagnoses, prognoses and interventions based on the physical therapist's examination and evaluative process. In veterinary medicine, only a veterinarian can make a veterinary diagnosis, and it is the veterinarian’s responsibility to coordinate all phases of treatment and aftercare.

VETERINARY REHABILITATION Certification programs in equine physical rehabilitation are offered to veterinarians, veterinary technicians, physical therapists, chiropractors and physical therapist assistants by these organizations: the Animal Rehab Institute in Loxahatchee, Florida or the University of Tennessee in Knoxville, Tennessee.

Figure 1: Functional Electrical Stimulation

that fall within the realm of veterinary physical therapy and are supported by evidence-based research. These techniques are based in movement and locomotor sciences and the underlying concept of motor control, which is central to understanding rehabilitation from musculoskeletal injuries.

Equine rehabilitation is the application of an all-new diagnostic algorithm to our horses. It focuses upon soft tissues rather than Who should be doing the rehabilitation work? The person to bone and joint. It involves special tests that allow for determination oversee the protocol should be the veterinarian; however, the of specific tendinopathies and soft tissue abnormalities. The use of veterinarian should seek advice from those who know the science objective outcome measures will be absolutely necessary if this area of rehab and look to develop a team approach. The veterinarian is to grow. The emphasis in rehabilitation therapy is on meeting will not be the one doing the rehab protocol on a daily basis but goals that are functional for the patient. The goals of rehabilitation rather the one to help organize the general protocol. The owner include the restoration, maintenance and promotion of optimal or a technician will typically be doing the day-to-day work of the function and quality of life as they relate to movement disorders. rehabilitation, not unlike in the human health care system.

Equine rehabilitation is in its infancy. It is an exciting time, but we Rehabilitation takes time. In chronic cases, it takes time for the must progress carefully and look toward those with experience in problem to show up; therefore, it is going to take time to fix the this specific area. However, this does not mean that we ignore those problem. Not only does the primary problem need to be solved, who have been working in the field of rehabilitation for decades. but rehabilitation to improve the secondary problem of poor These individuals may not have formal background in equine biomechanics must also be solved so that there is a lower chance rehabilitation but have learned by trial and error what works and of re-injury. In acute cases, such as trauma, the time required for what doesn’t. These people can include veterinarians that have rehabilitation may be shorter if there are no secondary mechanical had a special interest in rehabilitation over the years, but can also problems that inhibit the healing process. include technicians who have been working on the race track or with performance horses in charge of the rehabilitation protocols. Rehabilitation utilizes manual therapies and therapeutic modalities.

Some basic research has been done on some modalities, but more During rehabilitation from lameness, physical therapy may include work is necessary to determine the effects these therapies have manual techniques, an exercise-based conditioning program to on the equine body. Through this type of basic research, the activate and strengthen specific muscles, aquatic therapy, and ground work will be laid not only to determine when it would be the use of various modalities such as therapeutic ultrasound and appropriate to use a particular therapy but also the intensity and laser. This article addresses specific areas of equine rehabilitation 4 The Practitioner Issue 4 • 2018

duration of treatment. For instance, under what circumstances should therapeutic ultrasound be used? Electrical stimulation (Figure 1)? Shockwave? Magnetic or electromagnetic therapy?

Massage? It will be the combination of basic research and clinical experience that will be needed to develop protocols for these modalities.

How will the process look? The process starts with an accurate diagnosis and assessment of the injury. In addition, an overall assessment of the horse’s secondary or compensatory problems must be performed. This should also include an assessment of hoof balance. Making an accurate diagnosis may require different imaging modalities including MRI, CT, ultrasonography and radiography.

In addition, a physiologic imaging modality, like thermography (Figure 2) or scintigraphy, may be very useful in identifying the secondary problems.

The next step is to determine the most appropriate therapy and determine if any modality will help the healing process. This must be followed by development of a protocol to restore function. This is not merely healing of the original injury but restoration of range of motion and strength. This would require correction of secondary issues as well as correction of hoof balance issues. This will require the development of new techniques to measure range of motion of horses as well as measuring strength. This is not to mention the difficulties of determining the healing of secondary issues.

Rehabilitation of performance horses is unique because the rider position must also be part of the solution. Rehabilitation requires the integration of many people to make it work, which is not unlike most areas of veterinary medicine. Some of these people that will need to understand the rehabilitation process include the owner, trainer, saddle fitter, farrier, nutritionist and barn manager.

Rehabilitation is not just the use of machines and modalities-it is the knowledge of how to use them in an appropriate protocol.

Treatment and Prevention of Equine Back Pain

Back pain is recognized as a common and important cause of poor performance in athletic horses, which has stimulated clinical and research interest in the diagnosis and treatment of equine back pain. There is extensive literature describing the clinical manifestations, pathoanatomical diagnoses, treatment and rehabilitation of back pain in people. It is known that lower back pain is associated with persistent inhibition of activity in the deep spinal stabilizer muscles, specifically the multifidus and transversus abdominis. Within a matter of days after an injury, such as a herniated disc, neurogenic atrophy is evident in the multifidi at the affected spinal level on the ipsilateral side.1 After back pain resolves, the atrophied muscles do not usually resume normal activation patterns unless specific therapeutic exercises are prescribed. The use of these exercises has been shown to reduce the one-year recurrence rate from 80 percent to about 30 percent.2 Back pain in horses appears to follow the human model in that affected horses have atrophy of multifidus on the affected side(s) and resolution of back pain is not necessarily accompanied by reactivation or hypertrophy of multifidus. This is in contrast to the response of the superficial and easily palpable longissimus muscle which may go into spasm as it attempts to compensate for the loss of spinal stability; however, the attachments of longissimus dictate that it is more effective in moving the spine than in stabilizing the individual intervertebral joints. Loss of the stabilizing influence of multifidus allows micromotion of the intervertebral joints which predisposes to the development of degenerative joint disease.

Anecdotal reports suggest that dynamic mobilization exercises (baited stretches) performed in flexion or lateral bending are beneficial in athletic horses with back pain. The principle of these exercises is that a bait, such as a piece of carrot, is used to entice the horse to move the chin to a specific position.3 The exercises are performed in cervical flexion with the chin moving to the chest; between the carpi or between the fore fetlocks; in cervical extension; and in lateral bending to the left and right sides with the chin moving to the girth, hip, flank or tarsus/hind fetlock.

The beneficial effect of these exercises is based on the need to activate the deep spinal musculature (multifidi) to stabilize the thoracolumbar-sacral spine as the head and neck assume a variety of extreme positions. The benefits have been confirmed in two research studies both of which used ultrasonography to show significant increases in cross-sectional area of the multifidus muscles in response to performing baited stretches regularly over a period of time. In the first study, eight school horses performed baited stretches five days a week for three months without any other exercise. There were significant increases in multifidus CSA bilaterally at T10, T12, T14, T16, T18 and L5, together with significant improvements in left:right symmetry at each of these spinal levels.4 A second study conducted in Thoroughbreds in race training found a significant increase in multifidus CSA at

Figure 2: Thermography - Heat application

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T16 in horses that performed baited stretches daily for six weeks, in addition to their regular training program, but not in controls subjected to the same training program without baited stretches.5 It is recommended that baited stretches be used both prophylactically and therapeutically. Three to five daily repetitions of each exercises appears to be adequate to restore or maintain activity and strength of multifidus.

Proprioceptive Stimulation

Following recovery from orthopedic injury, gait deficits may persist due to soft tissue stiffness, muscle atrophy, altered neuromotor coordination patterns or inhibition of specific muscles. These deficits do not necessarily resolve spontaneously with normal exercises and training.6 During rehabilitation, physical therapy is used to restore function in terms of range of joint motion (ROM), muscle activation, and muscular Figure 3: Thermography - Vibrating plate coordination and strength. Muscle strength and endurance are improved by increasing the intensity or number of repetitions, respectively, of exercises targeted at recruiting specific muscles.

Sometimes a muscle becomes inhibited as a consequence of a There were no changes in peak vertical force or in the degree minor trauma involving pain or capsular distension. This type of fetlock extension when trotting over poles, suggesting that of inhibition usually involves the deep stabilizing muscles of a loading of the musculoskeletal tissues is comparable with that joint rather than the prime movers. The result is joint instability associated with trotting on level ground at the same speed. that predisposes to degenerative changes due to micromotion of This makes it unlikely that trotting over poles will jeopardize the joint. A well-documented example in the human field is the the recovery process by over-loading the limbs. Peak forelimb development of patellofemoral pain following a minor pathology, braking force increased, and the transverse impulse changed such as distension of the femorotibial joint. This leads to altered from being directed medially when trotting on level ground to knee joint proprioception and changes in the activation sequence laterally directed when trotting over poles. This was interpreted as of the different heads of quadriceps femoris. Vastus medialis a mechanism to enhance balance and suggests that the adductor obliquus, which is a deep stabilizer of the knee, shows delayed musculature is being recruited. onset of activity leading to a wide range of effects including maltracking of the patella and loss of strength in the external Unlike the use of proprioceptive stimulation devices in which rotators and abductors of the hip. Evidence-based studies the effects decrease over time due to habituation, the horse is support the use of physiotherapeutic treatment targeting vastus required to elevate the hooves to ensure clearance whenever medialis obliquus by use of taping, bracing and various forms of poles are present. The need to raise the limbs sufficiently to clear the poles and to adjust the step length, so the hooves are therapeutic exercise.7 placed accurately, also requires visuomotor coordination, which In horses, little is known about the deep stabilizing musculature suggests an application in rehabilitating neurological cases. in locations other than the spine, and there are no evidence-based reports of the effect of therapeutic exercises on specific muscles CONCLUSION in the limbs. However, there have been reports of the effect of Injections and surgery are the most common sports medicine techniques that change the range of motion of the joints through techniques used by veterinarians; however, veterinarians are stimulation of muscle activity (Figure 3). learning the difference between success and failure of these

Trot Poles

Trotting over poles is used therapeutically to restore full ranges of joint motion in the limbs. The kinematics and kinetics associated with trotting over poles on the ground (11 cm high) and raised poles (20 cm high) have been reported.8 Peak heights of the fore and hind hooves increased significantly and progressively from no poles (fore: 13.8±3.8 cm; hind: 10.8±2.4 cm) to low poles (fore: 30.9±4.9 cm; hind: 24.9±3.7 cm) and to high poles (fore: 41.0±3.9 cm; hind: 32.7±4.0 cm). Peak hoof heights when trotting over poles were higher than with tactile bracelets or leg weights. All joints of the fore and hind limbs contributed to the increase in hoof height through increased swing phase flexion.

treatments is aftercare. Rehabilitation is based on healing, improving flexibility and physical conditioning, strengthening the injured tissue, and then slowly returning to full activity.

References 1.

Hodges P, Holm AK, Hansson T, et al. Rapid atrophy of the lumbar multifidus follows experimental disc or nerve root injury. Spine 2006;31:2926-2933.Casey M (2013) A new understanding of oral and dental pathology of the equine cheek teeth. In Vet Clin Equine, 29, 301-324

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2. Hides JA, Jull GA, Richardson CA. Long-term effects of specific stabilizing exercises for first- episode low back pain.

Spine 2001;26:E243-248.

3.

Stubbs NC, Kaiser LJ, Hauptman J, et al. Dynamic mobilization exercises increase cross sectional area of musculus multifidus. Equine Vet J 2011;43:522-529.

4.

Stubbs NC, Clayton HM. Activate your horse's core. Sport Horse Publications, 2008:Mason, MI.

5. Tabor GF, Johansson C, Randle H. The effects of dynamic mobilization exercises on the multifidus muscle in thoroughbred racehorses, In: 8th International Equitation Science Conference, Edinburgh, Scotland, 2012:64.

6. Van Harreveld PD, Lillich JD, Kawcak CE, et al. Clinical evaluation of the effects of immobilization followed by remobilization and exercise on the metacarpophalangeal joint in horses. Am J Vet Res 2002;63:282-288.

7. Crossley K, Bennell K, Green S, et al. A systematic review of physical interventions for patellofemoral pain syndrome.

Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 2001;11:103-110.

8. Brown S, Stubbs N, Kaiser L, et al. Swing phase kinematics and kinetics of horses trotting over poles. Equine Vet J, DOI: 10.1111/evj.12253, Epub 2014 Apr 9

Tracy A. Turner, DVM, MS, DACVS, DACVSMR Dr. Tracy Turner received his DVM degree from Colorado State University in 1978 and interned at the University of Georgia. He completed a surgical residency and Master's degree at Purdue University. He has served on the faculties of the University of Illinois, University of Florida and the University of Minnesota. He joined Anoka Equine Clinic in Elk River, Minnesota in 2004, where he practices in sports medicine, lameness and surgery. Dr. Turner's primary area of research interests has focused on equine lameness with particular interest in equine podiatry and thermography. He has spoken nationally and internationally on lameness topics. He has written more than 100 peer reviewed manuscripts, more than 250 non-peer reviewed papers, and more than 30 book chapters on equine lameness, podiatry and thermography.

Dr. Turner is a Diplomate of the American College of Veterinary Surgeons, a Diplomate of the American College of Sports Medicine and Rehabilitation, and is a Fellow of the American Academy of Thermology. He is an active member of the AVMA, AAEP and the American Horse Council, and he is currently the vice president of the Minnesota Horse Council.

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NAVICULAR BURSA LAURA M. RIGGS | DVM, Ph.D., DACVS-LA, DACVSMR BRITTA LEISE | DVM, Ph.D., DACVS-LA

Introduction

Navicular disease/syndrome is a term that has been used to clinically describe pain related to the caudal one-third of the foot or heel region.

Although historically thought to be a single disease/condition, it is currently believed that a number of clinical conditions of different etiologies give rise to the pain associated with the navicular apparatus. These conditions often result in mild to moderate bilateral forelimb lameness that is insidious in onset and slowly progressive; however, the lameness can also be quite severe, acute in onset and affect only one foot. A positive response to analgesia of the navicular bursa indicates that lameness may be due to pain associated with the navicular bone, navicular bursa or a lesion of the deep digital flexor tendon.

Figure 1: Sagittal section of the navicular region. P2- 2nd phalanx, P3- 3rd phalanx, DDFT- deep digital flexor tendon. (Photo courtesy of Dr. Britta Leise)

Local treatment of diseases of the podotrochlear apparatus may be indicated in deep digital flexor tendon (DDFT) tendinopathy, collateral and distal sesamoidean desmopathy, and in degenerative bone disease of the navicular bone. These conditions are generally accompanied by synovitis of the navicular bursa, which may benefit directly from intrabursal medication. Patients with such injuries have been shown to respond better to medication of the navicular bursa than of the distal interphalangeal (DIP) joint.

Several techniques for injection of the navicular bursa will be described. Techniques using radiography and ultrasonography to ascertain correct needle placement during bursocentesis will also be described.

Some practitioners have questioned the potentially detrimental effects of penetrating the DDFT during bursocentesis and alternative approaches have been described to avoid the DDFT.

Anatomy of the navicular region

Navicular bone: Also known as the distal sesamoid bone (Figure 1).

• Proximal boarder - Portion of the navicular suspensory (collateral) ligaments attach here.

• Distal boarder - Has an elongated facet for articulation with P3.

• Flexor surface - Covered with fibrocartilage to allow for sliding of the DDF tendon. The midsagittal ridge is located in the middle of this surface.

The bone has multiple synovial invaginations (once called vascular channels).

Ligamentous support of the navicular bone: • Paired navicular suspensory (collateral) ligaments - Arise from the proximal phalanx (P1) on each side of the distal end of P1, just dorsal to the collateral ligament of the PIP joint.

These attach to the proximal aspect and extremities or “wings” of the navicular bone. The Impar ligament attaches the distal boarder of the navicular bone to the flexor surface of P3 palmar to the insertion of the DDF tendon.

Navicular bursa: Located between the DDF tendon and the flexor surface of the navicular bone. It extends proximal and distal to the navicular bone and functions to help cushion the movement of the tendon against the bone.

Deep digital flexor tendon: Courses from the proximal aspect of the limb over the flexor surface of the navicular bone and then attaches to the distal aspect of P3.

8 The Practitioner Issue 4 • 2018

An 18-20 gauge, 3.5 inch (9 cm) spinal needle is inserted just proximal to the lateral cartilage of the distal phalanx – between the palmarolateral border of the middle phalanx and the lateral border of the DDFT – and proximal to the navicular position.

Take care to insert the needle palmar to the palmar digital neurovascular bundle at an angle of approximately 45° to the solar plane of the foot in the frontal plane of the limb. At this point, the tip of the needle should be visualized with the ultrasound while the proximal border of the navicular bone, the lateral lobe of the DDFT and the lateral CSL are in the same field.

The needle is then advanced within the plane of the ultrasound beam in a proximolateral to distomedial oblique trajectory in the frontal plane of the limb under ultrasound guidance. Care should be taken to avoid penetration of the DDFT and the CSL as the needle is advanced to reach the palmar surface of the navicular bone.

Radiographic-guided injection from the lateral aspect of the limb Figure 2: Lateral radiographic view of a navicular bursa injection through the DDFT (Photo courtesy of Dr. Laura Riggs)

Traditional approach to injection of the navicular bursa through the DDFT

The navicular bursa is more difficult to inject than other synovial structures, and accurate needle placement is essential. For this reason, radiographic control is necessary in this described technique to insure proper placement. The needle should be placed at the middle of the flexor surface of the navicular bone.

A needle placed too far proximally may inadvertently be placed in the proximal palmar pouch of the distal interphalangeal joint or less commonly the flexor tendon sheath. If the needle enters too distally it may enter the joint through the distal palmar pouch.

In this approach, an 18-20 gauge, 3.5 inch (9 cm) spinal needle is inserted along the palmar midline, immediately proximal to the hairline and directed parallel to the sole until the needle contacts bone. The needle is most often advanced approximately 5-6 cm.

If it can be advanced farther than this, it is likely not in the correct position. Placement of the toe in a wooden block can facilitate this approach and aid in aseptic technique. Correct placement can be confirmed radiographically before injection.

The injection begins on the lateral or medial lobe of the DDFT (depending on injection side) and an 18-20 gauge, 3.5 inch (9 cm) spinal needle is inserted approximately 1–2 cm through the above described location in a palmaroproximolateral‐ palmarodistomedial oblique (Pa30Pr30L‐PaDiMO) directed approximately 30–40° to the horizontal plane as viewed from the palmar aspect of the foot and angled towards a 10 o'clock (right fore) or 2 o'clock (left fore) position on the limb when viewed from above the hoof. A lateromedial radiograph is then obtained, and the angle and direction of the needle are adjusted.

The needle is then inserted further until positioned, based on a final radiograph, in a site consistent with the proximal recess of the navicular bursa.

Treatment of navicular bursa

Corticosteroids (methylprednisolone acetate, triamcinolone acetonide and betamethasone sodium phosphate) have been injected into the navicular bursa with varied results. These medications have often been combined with hyaluronic acid to decrease the clinical signs associated with navicular syndrome. More recently, Interleukin-1 receptor antagonist protein (IRAP) has been used to treat inflammatory processes such as osteoarthritis and navicular syndrome. This treatment has been reported to be very effective in treatment of cases in which navicular bursitis, adhesions between the DDFT, and navicular bone or DDFT lesions have been reported. Regardless of treatment, the direct injection of the navicular bursa affords the practitioner with a valuable treatment option for With the foot held steady in flexion in a navicular block, a 5–8‐ navicular syndrome.

Mhz microconvex ultrasound transducer is placed longitudinally against the palmar aspect of the DDFT in the distal aspect of the References pastern region. The probe is tipped 45° laterally, thereby causing 1. Johnson SA, Barrett MF, Frisbie DD. Additional it to lie obliquely, axial to the lateral collateral cartilage with the palmaroproximal-palmarodistal oblique radiographic beam pointing dorsally. The lateral lobe of the DDFT, the lateral projections improve accuracy of detection and collateral sesamoidean ligament (CSL), and the lateral aspects characterization of equine flexor cortical lysis. Vet Radiol of the navicular bone and middle phalanx are visualized (see Ultrasound. 2018 Jul;59(4):387-395.

Figure 2).

Ultrasound-guided, tendon-sparing, lateral approach to injection of the navicular bursa

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2. Groom LM, White NA 2nd, Adams MN, Barrett JG. Accuracy of open magnetic resonance imaging for guiding injection of the equine deep digital flexor tendon within the hoof. Vet Radiol Ultrasound. 2017 Nov;58(6):671-678.

3. Olive J, Videau M. Distal border synovial invaginations of the equine distal sesamoid bone communicate with the distal interphalangeal joint. Vet Comp Orthop Traumatol.

2017 Mar 20;30(2):107-110.

4.

Nottrott K, De Guio C, Khairoun A, Schramme M. An ultrasound-guided, tendon-sparing, lateral approach to injection of the navicular bursa. Equine Vet J. 2017 Sep;49(5):655-661.

5. Perrin R, Diguet AC, Cantet P, Bailly C, Brogniez L, Dugdale A, Nisolle JF, Vandeweerd JM. Ex Vivo Assessment of an Ultrasound-Guided Injection Technique of the Navicular Bursa in the Horse. Anat Histol Embryol.

2016 Dec;45(6):450-456.

Laura Riggs, DVM, Ph.D., DACVS-LA, DACVSMR Louisiana State University Dr. Laura Riggs is an associate professor and the service chief of equine surgery in the Department of Veterinary Clinical Sciences at Louisiana State University. She is a 2001 graduate of the University of Tennessee, College of Veterinary Medicine. Following graduation, she completed a large animal rotating internship and surgery residency at the University Of Georgia College Of Veterinary Medicine. In 2007, she became a Diplomate of the American College of Veterinary Surgeons. The same year she completed a Ph.D. in veterinary physiology at the Unversity of Georgia. In 2016, she became a Diplomate of the American College of Veterinary Sports Medicine and Rehabilitation. Since 2008, Dr. Riggs has been a member of the clinical faculty in the Veterinary Teaching Hospital at Louisiana State University, where she is actively involved with clinical, teaching and research activities at the Equine Health Studies Program.

Britta Leise, DVM, Ph.D., DACVS-LA Louisiana State University Br it ta L e i se , DVM, Ph .D., DACVS-LA is a 2002 graduate from the Louisiana State University School of Veterinary Medicine. She completed her internship in large animal medicine and surgery at the University of Georgia from 2002-2003 and an equine surgery residency at LSU in 2007. She was a clinical instructor in equine emergency and critical care at The Ohio State University where she also completed a Ph.D. in Comparative and Veterinary Medicine. She is currently an assistant professor of equine surgery at Louisiana State University. Dr. Leise’s research interests include equine laminitis and conditions of the foot, wound healing, and inflammatory processes associated with sepsis/SIRS.

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CLINICAL APPLICATIONS OF LAMINITIS RESEARCH LAURA M. RIGGS | DVM, Ph.D., DACVS-LA, DACVSMR BRITTA LEISE | DVM, Ph.D., DACVS-LA

Pathophysiology of Laminitis

Laminitis is an extremely complex disease and has been associated with inflammatory conditions and endotoxemia. Several primary conditions are seen preceding the clinical signs of laminitis including strangulating gastrointestinal disorders, enterocolitis, pneumonia, metritis and grain overload, equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), toxic insults, and those with mechanical overload due to severe contralateral lameness. Over the years, researchers have attempted to find one theory that will explain how this devastating disease occurs in the horse; however, with increasing knowledge, it is now becoming accepted that the numerous proposed mechanisms are interconnected with each other. Four main mechanisms are believed to play a role in laminitis: inflammation and extracellular matrix (ECM) degradation, endothelial and vascular dysfunction, endocrine/metabolic derangements, and mechanical forces. Inflammatory mediator production, leukocyte migration and increases in degrading matrix metalloproteases have all been documented in the lamina of affected horses early in the developmental periods of this disease. Platelet activation, microthrombi formation and the production of vasoactive mediators are also known to occur in the lamina of a horse affected with laminitis. Changes in digital and laminar blood flow is known to occur throughout the developmental phases, and, although not thought to play as important of a role as previously thought, vascular derangements/alterations most likely have a role in the development of laminitis.

analgesics, anti-thrombotics, vasodilators, anti-oxidants, antiendotoxic therapies, cyrotherapy and mechanical support.

Treatment of the primary disease is by far the best way to prevent the development of laminitis. This can involve the use of various therapies depending on possible inciting causes such as prompt surgical correction of strangulating intestinal lesions, antibiotic administration for treatment of bacterial-induced pneumonia, diarrhea, metritis, dietary management of EMS, pergolide for management of PPID, and treatment of and pain management for contralateral limb lameness. Dietary changes for horses with EMS include limiting or eliminating pasture grazing (particularly in early spring time of the year), and removing grain from their diet or feeding them a low carbohydrate feed such as Purina Well Solve that was designed for horses with insulin resistance. In obese horses, weight loss may be facilitated by the administration of levothyroxine sodium (ThyroL™) starting at 0.1 mg/kg of BW PO q24h. Horses with PPID should be treated with Pergolide (Prescend™), a dopamine receptor agonist which acts to restore the inhibition of the pars intermedia, down regulating activity in this area and decreasing ACTH production. The starting dose is 1 mg per day for adult horses (450kg horse) and can be increased up to 3 to 5 mg/day if no significant response is seen after 30 days.

Endotoxemia has long been known to be a risk factor for the development of laminitis, and many sepsis cases are a result of gastrointestinal disease. This increases the risk of having or developing endotoxemia. It is important to treat or prevent endotoxemia from occurring in these patients, and the neutralization of endotoxins through the administration of Polymyxin B has been found to be an effective treatment in horses.

Polymxin B is a cationic polypeptide antibiotic that has been shown to bind lipid A and to neutralize the actions of endotoxin in-vitro. Clinically, polymyxin B is administered to horses at a dose of 2,000-6,000 U/kg every 12 hours, diluted in approximately 1 liter of polyionic fluid. This therapy is typically continued for approximately three days or until the signs of endotoxemia subside. Other preventions/treatments of endotoxemia that have been used in the horse with varying degrees of success include neutralization via hyperimmune serum or plasma, nonsteroidal anti-inflammatory drugs, DMSO and fluid therapy supportive care.

Inflammation is known to be present in the lamina from horses with both experimental and naturally occurring laminitis; therefore, it is only logical that anti-inflammatories are used in the treatment and prevention of laminitis. NSAIDs are by far the Successful treatments for laminitis are mostly aimed at prevention most common therapies used in the treatment and prevention with the goal of limiting or blocking the suspected causes. Therapies of laminitis. Typical doses for phenylbutazone range between include treatment of the primary disease, anti-inflammatories, 2.2 mg/kg and 4.4 mg/kg administered once or twice a day, and Figure 1: Classic stance of a horse affected by forelimb laminitis.

Treatment of Laminitis

12 The Practitioner Issue 4 • 2018

doses for flunixin meglumine range from 0.25 mg/kg IV q8h to 1.1 mg/kg IV q12h. Both of these NSAIDs are COX-1 and COX-2 inhibitors; therefore, they have the possibilities of resulting in side effects often associated with COX-1 inhibition, including gastrointestinal ulceration and renal papillary necrosis particularly when higher doses are utilized. Recent development of an equine COX-2-specific NSAID firocoxib would suggest that its use would have increased benefits over the traditional NSAIDs by having decreased gastrointestinal side effects while still being able to limit the up-regulation of COX-2 in the lamina reported with laminitis.

However with the negative cardiovascular effects associated with the use of COX-2-specific inhibitors in humans, there is some question of their use in horses early in the developmental stages of laminitis. Reported dosages are 0.1 mg/kg PO q24h or 0.09 mg/ kg IV q24h. It has also been suggested the first initial dosage be three times the recommended dose for the route of administration selected.

The use of antioxidants in horses with laminitis, such DMSO, has been used by some veterinarians for many years. DMSO has been used as an anti-inflammatory and free radical scavenger at 100 mg/kg of BW IV q12h diluted to a 10 percent solution. One retrospective study found that DMSO was used in 27 percent of laminitic cases, despite no controlled studies reporting to show definitive benefits of this therapy. The lack of benefit may be due to the fact that little evidence of oxidant stress has been found during the developmental phases of laminitis.

Digital hypothermia, also known as cryotherapy, has been used to ameliorate experimentally induced laminitis when applied during the developmental period. Continuous cryotherapy has been found experimentally to significantly reduce the up-regulation of degrading enzyme MMP-2 and reduce the expression of proinflammatory chemokines and cytokines in the early stages of laminitis after oligofructose administration. Suggested protocol for cryotherapy of the equine digit requires maintenance of hoof temperatures of around 5°C via submergence in an ice-water boot until the resolution of the primary disease. Initial studies involved the use of a modified wader-style boot that includes immersion of the limb from the upper metacarpus down to the digit, allowing for direct cooling of the hoof as well as cooling of the blood prior to entering the foot. Other methods of cooling the foot have been evaluated for temperature maintenance but have not been

Figure 2: Cryotherapy boot created with a 5-liter fluid bag filled with ice.

evaluated for their effectiveness in preventing laminitis. Clinically, an empty 5 liter fluid bag placed on the foot, filled with ice and then taped around the pastern, appears to be a relatively simple method of cyrotherapy (Figure 2). This method has been found to achieve hoof temperatures close to that of previous reports; however, it does not cool the blood in the metacarpal region and does require replenishment of ice at relatively frequent intervals.

Pain control is an essential component in managing laminitis and is important in the prevention of support limb laminitis secondary to non-weight bearing lameness. Previous discussion of the use of NSAID medications is also important for pain management in these cases. Phenylbutazone is by far the most common of the NSAIDs used but both flunixin meglumine and firocoxib have benefits as well. Gabapentin, a GABA analogue, has been used as a treatment for neuropathic pain in humans and horses, and the recommended dosages for the horse with laminitis are around 10-20 mg/kg PO q8-12h. The use of lidocaine as an IV CRI, although difficult to monitor in nonhospitalized patients, anecdotally has helped manage pain in more severe laminitic cases. Other effects of lidocaine that were initially thought to have benefit in laminitis, such as decrease in neutrophil migration, have been since disproven; however, administration of a loading dose (1.3 mg/kg administered over five to 15 minutes) followed by a CRI (0.05 mg/kg/minute) has been used for pain control. Since lidocaine is strongly protein bound, horses with low protein concentrations may need to have their dosages decreased as side effects, such as ataxia, may be more profound at normal dosages. To further take advantage of a multimodal approach to pain management, combining the use of lidocaine with morphine and ketamine in a CRI has resulted in positive response in several very painful patients. However, the use of this combination requires administration via a fluid pump and close monitoring; therefore, it is not useful in a farm setting. Other pain management medications that can be used include butorphanol and morphine (0.05 – 0.1 mg/kg IM q24h).

The addition of acepromazine (0.04 mg/kg) or detomidine have been used to decrease the excitement/agitation side effects seen with morphine administration. For horses having significant hind limb pain, epidural administration of pain medications has had significant benefits. Combination of morphine (0.2 mg/kg) and detomidine (30 μg/kg) q24h will give pain relief in many patients and help decrease the risk of systemic use of morphine.

Transdermal fentanyl has been reported to decrease pain scores in patients but demonstrated minimal improvement in lameness in horses with orthopedic pain and anecdotally has variable effects on pain relief in laminitic patients.

Vascular alterations – such as the production of vasoconstrictor agents such as serotonin, thromboxane A2 and endothelin-1 – and the presence of vasoconstriction (particularly venoconstriction) early in the developmental phases have been reported in horses with laminitis; therefore, the incorporation of vasodilators into therapeutic regimes is not unreasonable. Vasodilators that have been used in the treatment of laminitis in the horse include isoxuprine, nitroglycerine, acepromazine and pentoxifylline.

Isoxsuprine (0.6-4 mg/kg PO q12h) has reported α-adrenergic Continued on Page 20

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Creeping Indigo: A Closer Look at the Plant and the Toxins

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Continued from Page 13 antagonist effects, as well as β-adrenergic agonist effects, that should result in vasodilatation; however, oral administration has not been reported to produce any change in digital blood flow.

Acepromazine (0.04 mg/kg IM q6h), a phenothiazine tranquilizer, causes peripheral vasodilation through its α-adrenergic blockade and is one of the only used vasodilators that have been shown to increase digital blood flow in the horse. However, the duration of increased blood flow is variable from horse to horse, and the use of acepromazine is contraindicated in the sepsis/SIRS patient due to its profound hypotensive effects. Pentoxifylline (8-10 mg/ kg PO q12h), a non-selective phosphodiesterase inhibitor and rheologic agent, is believed to help improve the flow of blood through capillaries by increasing the deformability of the red blood cell membrane; however, an increase in blood flow has not been demonstrated in the horse. Despite these findings, pentoxifylline may still have a place in the treatment/prevention of laminitis in the horse through other mechanisms including anti-inflammatory (decreasing TNFα and IL-1β and neutrophil activation), anti-fibrotic and via MMP inhibition. In addition to the vasoconstrictive events reported to occur in the developmental phases of laminitis, microthrombosis of the laminar capillaries and platelet aggregation also occurs, and treatments aimed at these effects have been utilized by veterinarians. To help prevent formation of thrombi, anticoagulants such as aspirin (10-20 mg/kg PO q48h), which inhibits platelet aggregation, and heparin (40-80 IU/kg IV or SQ q8h), which down regulates the prothrombotic state, have been used in the treatment and prevention of laminitis.

Neutralization of or minimizing mechanical stresses is a very important factor in prevention and treatment of laminitis.

Minimal exercise/walking during the acute phase is strongly recommended. Any drastic change and application of shoes should be avoided during the acute stages, and it is recommended that three to four weeks have passed after the onset of laminitis before applying shoes to the horse’s feet. However if the toe is exceptionally long, it should be trimmed. Prevention of laminitis from a mechanical standpoint is aimed toward attempting to neutralize forces on the digit and include placing frog support, application of foot support such as polystyrene foam, and/ or bedding the horse on deep soft footing (such as sand) to minimize compressive forces on the digital cushion and decrease the tensile forces of the DDFT. Recommendations on what type of pad and location of application is variable. Some suggest that the entire sole is packed or padded to allow for equal weight bearing throughout the foot and oppose mechanical forces down the leg. Others will recommend that at least the frog is cushioned or supported. Some horses may not tolerate packing in the sole, particularly if rotation has already occurred. Placement of a rim cast or putting the horse in a sling to decrease weight-bearing loads through the digit may also have beneficial effects. It is also recommended to consider placement of a heel wedge (Redden shoe) to decrease tensile forces of the DDFT. In horses that continue to rotate or become refractory to all other therapy, a deep digital flexor tenotomy can be performed to help remove the mechanical pull from this source. This treatment, however, is saved for severe cases (significant rotation) due to

the negative effects of cutting the deep digital flexor tendon.

Tenotomies are most successful in cases where there is no significant bone pathology in P3 and no sinking, but rotation only. Complications associated with the procedure include infection, dehiscence, contraction/fibrosis of the tenotomy site before correction of rotation possibly requiring repeat procedure in the pastern region, and subluxation of the DIP joint resulting in arthritis of that joint.

Clinical history of horses presenting with laminitis can be variable depending on the initiating cause. Horses with acute laminitis usually have either had a recent illness, recent nonweight bearing lameness or recent changes in pasture grazing; however in some cases, an initiating cause may be difficult to determine. Treatment plans vary depending on the underlying causes and many other factors. It is important to use all available information to develop a treatment plan specifically for the individual patient.

Laura Riggs, DVM, Ph.D., DACVS-LA, DACVSMR Louisiana State University Dr. Laura Riggs is an associate professor and the service chief of equine surgery in the Department of Veterinary Clinical Sciences at Louisiana State University. She is a 2001 graduate of the University of Tennessee, College of Veterinary Medicine. Following graduation, she completed a large animal rotating internship and surgery residency at the University Of Georgia College Of Veterinary Medicine. In 2007, she became a Diplomate of the American College of Veterinary Surgeons. The same year she completed a Ph.D. in veterinary physiology at the Unversity of Georgia.

In 2016, she became a Diplomate of the American College of Veterinary Sports Medicine and Rehabilitation. Since 2008, Dr. Riggs has been a member of the clinical faculty in the Veterinary Teaching Hospital at Louisiana State University, where she is actively involved with clinical, teaching and research activities at the Equine Health Studies Program.

Britta Leise, DVM, Ph.D., DACVS-LA Louisiana State University Britta Leise, DVM, Ph.D., DACVS-LA is a 2002 graduate from the Louisiana State University School of Veterinary Medicine. She completed her internship in large animal medicine and surgery at the University of Georgia from 2002-2003 and an equine surgery residency at LSU in 2007. She was a clinical instructor in equine emergency and critical care at The Ohio State University where she also completed a Ph.D. in comparative and veterinary medicine. She is currently an assistant professor of equine surgery at Louisiana State University. Dr. Leise’s research interests include equine laminitis and conditions of the foot, wound healing, and inflammatory processes associated with sepsis/SIRS.

20 The Practitioner Issue 4 • 2018

Startwith it.

Staywith it.

™

For thirty years, Dr. Marvin Beeman, a founder of Littleton Equine Medical Center, has counted on Adequan® i.m. (polysulfated glycosaminoglycan) for his patients. He even uses it on his own horse, Foxy, his beloved third-generation homebred mare. Adequan® has helped keep Foxy perfoming into her teens—so together, they’re still galloping strong.

Only Adequan® may help improve joint function by: 1, 2 REVERSING the disease cycle REPAIRING cartilage RESTORING joint lubrication and REDUCING inflammation to help keep joints moving and horses performing.

Thirty years of love and Adequan i.m. says it all.

When you and your veterinarian start with Adequan® i.m. and stay with it, your horse may enjoy greater mobility over a lifetime.3, 4

®

Ask your veterinarian if Adequan® is the right choice for your horse. Visit adequan.com.

BRIEF SUMMARY: Prior to use please consult the product insert, a summary of which follows: CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. INDICATIONS: Adequan® i.m. is recommended for the intramuscular treatment of non-infectious degenerative and/or traumatic joint dysfunction and associated lameness of the carpal and hock joints in horses. CONTRAINDICATIONS: There are no known contraindications to the use of intramuscular Polysulfated Glycosaminoglycan. WARNINGS: Do not use in horses intended for human consumption. Not for use in humans. Keep this and all medications out of the reach of children. PRECAUTIONS: The safe use of Adequan® i.m. in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. For customer care or to obtain product information, visit www.adequan.com. To report an adverse event please contact American Regent, Inc. at (800) 734-9236 or email pv@luitpold.com.

Please see Full Prescribing Information at www.adequan.com.

1. Adequan® i.m. [package insert]. Shirley, NY: Luitpold Animal Health; 2008; 2017.

2. Burba DJ, Collier MA, DeBault LE, Hanson-Painton O, Thompson HC, Holder CL: In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondral defect model. J Equine Vet Sci 1993; 13: 696-703.

3. McIlwraith CW, Frisbie DD, Kawcak CE, van Weeren PR. Joint Disease in the Horse. St. Louis, MO: Elsevier, 2016; 33-48.

4. Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY. Articular chondrocyte apoptosis in equine osteoarthritis. The Veterinary Journal 2003; 166: 52-57.

Adequan and the Horse Head design are registered trademarks of American Regent, Inc. © 2018, American Regent, Inc. PP-AI-US-0184 10/2018

THERAPEUTICS FOR INFECTIOUS ENDOMETRITIS: A Clinical Perspective RYAN A. FERRIS | DVM, MS, DACT

TREATMENT OF BACTERIAL ENDOMETRITIS Mares diagnosed with bacterial endometritis can be divided into acute and chronic infections. While these terms have multiple meanings, for this discussion acute endometritis will describe cases in which mares are exposed to bacterial pathogens and an infection develops. The term chronic endometritis is going to be used in cases where acute bacterial endometritis is detected, appropriate therapy initiated yet the infection continues to persist despite treatment.

Acute Bacterial Endometritis

In cases of acute bacterial endometritis, mares appear systemically healthy, may have intrauterine fluid present on transrectal ultrasound examination, vaginal discharge or fluid in the vaginal vault. On speculum examination, a reddened cervix and cervical discharge can be observed. Normally, the mare’s uterus can rapidly clear bacteria or fungi without development of an infection; however, any breakdown in the defense mechanisms of

the reproductive tract predisposes a mare to a uterine infection.

Increased numbers of bacteria reaching the endometrium due to abnormalities of the perineum, vestibulovaginal seal or cervix may result in development of infections. A decreased ability of the mare’s uterus to contract reduces the clearance of fluid and contaminants from the uterus. Finally, a breakdown in the innate immune system reduces the response toward pathogens in the uterus. All of these factors individually or in combination can contribute to development of bacterial endometritis.

Diagnosis of acute endometritis is usually performed via doubleguarded uterine culture swab and cytology brush. This allows for detection, identification and characterization of microbial organisms and evaluates the uterine lumen for the presence of polymorphic neutrophils (PMNs), which are indicative of active inflammation. The results of the culture and cytology can be interpreted as: •

A positive culture result with a positive cytology result is diagnostic of a uterine infection.

TABLE 1. ANTIBIOTICS FOR INTRAUTERINE THERAPY Medication

Dosage, Route, Frequency

Indications

Amikacin sulfate (Amiglyde-V®) (250 mg/ml)

1-2 grams; buffer with 10 to 20 mls sodium bicarbonate (8.4 %) then qs to 60 mls with sterile saline

Antibiotic (Gram-negative spectrum)

Ampicillin (1 gm vial)

1-2 grams, reconstitute in 60 mls sterile saline

Antibiotic (Gram-positive spectrum primarily)

Ceftiofur (Naxcel®)

1 gram, reconstitute with 20 to 60 mls sterile water

Antibiotic (broad spectrum)

Gentamicin (100 mg/ml)

1-2 grams; buffer with 10 to 20 mls of 8.4 % sodium bicarbonate

Antibiotic (Gram-negative spectrum)

Penicillin (Potassium) (5 million units/ vial)

5 million units, reconstitute in 60 mls sterile saline

Antibiotic (Gram-positive spectrum)

Penicillin (Procaine) (300,000 units per ml)

15 mls, dilute to 60 mls in sterile saline

Antibiotic (Gram-positive spectrum)

Ticarcillin/Clavulanic acid (Timentin®) (3.1 gm per vial)

3.1 grams, reconstitute to 60 mls with sterile saline

Antibiotic combination; clavulanate blocks penicillinase; used for gram positive organisms and Pseudomonas aeruginosa

22 The Practitioner Issue 4 • 2018

TABLE 2. ANTIBIOTIC AND NON-ANTIBIOTIC COMBINATIONS FOR THE TREATMENT OF BIOFILM ASSOCIATED BACTERIAL ENDOMETRITIS IN MARES Tris EDTA- final concentration in the syringe should be 50 mM Tris and 3.5 mM EDTA Note: Tris-EDTA and Tricide are similar; however Tricide is not equivalent to Tris-EDTA in regards to bacterial killing To make Tris-EDTA: 16oz bottle of Dechra Triz-EDTA crystals; add 8 oz of sterile water (this is different than the bottle instructions).

The 2x concentration of Tris-EDTA solution will be further diluted by the antibiotics below to the proper final concentration.

Antibiotic

Drug Amount

Tris EDTA

Amikacin (250 mg/ml)

4 mls (1 gram)

30 mls

Ceftiofur (1 gram reconstituted in 20 mls)

20 mls (1 gram)

30 mls

Ciprofloxacin (10 mg/ml)

40 mls (400 mg)

40 mls

QS

Final volume

Notes:

16 mls sterile fluid (Saline, LRS, Sterile 60 mls H2O) 10 mls sterile fluid 60 mls (Sterile H2O)

10 mls of 8.4% sodium bicarbonate should be added to the amikacin

0

Split between two syringes

80 mls

H2O2- 1% final concentration in the syringe A 3% stock solution is available at many drug stores and veterinary distributors Antibiotic

Drug Amount

H2O2

QS

Final volume

Amikacin (250 mg/ml)

4 mls (1 gram)

20 mls

26 mls sterile fluid (Saline, LRS, Sterile 60 mls H2O)

Ciprofloxacin (10 mg/ml)

40 mls (400 mg)

20 mls

0

Notes: 10 mls of 8.4% sodium bicarbonate should be added to the amikacin

60 mls

DMSO - 30% final concentration in the syringe 99% stock solution is used for calculations below Antibiotic

Drug Amount

DMSO

QS

Final volume

Ceftiofur (1 gram reconstituted in 20 mls)

20 mls (1 gram)

20 mls

20 mls sterile fluid 60 mls (Sterile H2O)

Ciprofloxacin (10 mg/ml)

40 mls (400 mg)

20 mls

0

•

A negative culture with a positive cytology result suggests inflammation not caused by an infectious agent (postmatinginduced endometritis, pneumovagina, urine pooling); however, intrauterine bacteria are not always cultured using standard techniques. If a significant cause of primary inflammation cannot be identified, further diagnostics, such as a low volume lavage or PCR for microbial DNA, should be performed. In some cases, bacterial and fungal organisms may be seen on a cytology slide, and the uterine culture results are negative.

•

A positive culture result with a negative cytology result may be observed with some uterine bacterial infections (e.g.

Escherichia coli), which may not always be associated with an inflammatory response.

If the culture is from one of the bacterial genus known to be pathogenic in the equine uterus, treatment is always warranted; however, there is a long list of bacteria with questionable pathogenicity. These organisms may be associated with an infection when there is a heavy growth and with evidence of clinical disease (positive cytology, intrauterine fluid or history of short cycling). The therapeutic plan is to aid the uterus in clearing infectious agents and inflammatory debris.

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Notes:

60 mls

For mares with large volumes of intrauterine fluid, a uterine lavage will be performed prior to antibiotic treatment. The goal of the lavage with 0.9 percent saline or lactated Ringer’s solution is to reduce the number of infectious organisms, remove inflammatory debris from the uterus, and potentially enhance luminal defense mechanisms by inducing local irritation and influx of PMNs into the uterine lumen. We will typically treat these mares with three days of intrauterine therapy based on antimicrobial susceptibility patterns (Table 1). Naxcel is our antibiotic of choice for empirical therapy, if therapy is initiated before antimicrobial susceptibility is returned. Ecbolics such as oxytocin (5 to 20 IU administered IM or IV) or cloprostenol (250 µg IM) should not be given during the lavage or shortly after the antibiotic infusion as this may cause the majority of the antibiotics to be immediately evacuated from the uterus. We try to collect our culture and cytology samples in early estrus so that if bacterial endometritis is detected therapy can be initiated and the mare still bred on the same estrus cycle.

Part of the treatment plan needs to address issues with perineal conformation with procedures such as a Caslick, perineal body reconstruction or cervical laceration repair. Any mare with less than two-thirds of the vulva below the pelvic brim or greater than 10° of angulation of the vulva warrants placement of a Caslick.

Severe cases with minimal to no vulva below the pelvic brim

FLORIDAAEP |

@FLORIDA_VMA | The Practitioner 23

Tildren

®

(tiludronate disodium) BISPHOSPHONATE DRUG FOR INTRAVENOUS INFUSION. For use in horses only WARNINGS Do not use in horses intended for human consumption. NSAIDs should not be used concurrently with Tildren®. Concurrent use of NSAIDs with Tildren® may increase the risk of renal toxicity and acute renal failure.

HUMAN WARNINGS Not for human use. Keep this and all drugs out of the reach of children. Consult a physician in case of accidental human exposure.

CAUTION Federal law restricts this drug to use by or on the order of a licensed veterinarian.

INDICATION Tildren® is indicated for the control of clinical signs associated with navicular syndrome in horses.

CONTRAINDICATIONS Do not use in horses with known hypersensitivity to tiludronate disodium or to mannitol. Do not use in horses with impaired renal function or with a history of renal disease. Bisphosphonates are excreted by the kidney; therefore, conditions causing renal impairment may increase plasma bisphosphonate concentrations resulting in an increased risk for adverse reactions.

PRECAUTIONS Approximately 30-45% of horses administered Tildren® will demonstrate transient signs consistent with abdominal pain (colic). Horses should be observed closely for 4 hours postinfusion for the development of clinical signs consistent with colic or other adverse reactions. Colic signs can last approximately 90 minutes and may be intermittent in nature. Hand walking the horse may improve or resolve the colic signs in many cases. If a horse requires medical therapy, non-NSAID treatments should be administered due to the risk for renal toxicity. Avoid NSAID use.

Horses should be well hydrated prior to administration of Tildren® due to the potential nephrotoxic effects of Tildren®.

Tildren® should be used with caution in horses receiving concurrent administration of other drugs that may reduce serum calcium (such as tetracyclines) or whose toxicity may exacerbate a reduction in serum calcium (such as aminoglycosides).

Horses with HYPP (heterozygous or homozygous) may be at an increased risk for adverse reactions, including colic signs, hyperkalemic episodes, and death.

The safe use of Tildren® has not been evaluated in horses less than 4 years of age.

Bisphosphonates should not be used in pregnant or lactating mares, or mares intended for breeding. Bisphosphonates have been shown to cause fetal developmental abnormalities in laboratory animals.

DOSAGE AND ADMINISTRATION A single dose of Tildren® should be administered as an intravenous infusion at a dose of 1 mg/kg (0.45 mg/lb). The infusion should be administered slowly and evenly over 90 minutes to minimize the risk of adverse reactions. Maximum effect may not occur until 2 months post-treatment.

For ADMINISTRATION INSTRUCTIONS (preparation of the reconstituted solution (20mg/mL) and preparation of the solution for infusion) and for complete product information, please read the insert contained within the product packaging.

STORAGE Sterile powder (not reconstituted): Store at controlled room temperature 68°F-77°F (20°C-25°C). After preparation, the infusion should be administered either within 2 hours of preparation, or it can be stored for up to 24 hours under refrigeration at 36°F-46° F (2°C-8°C) and protected from light.

HOW SUPPLIED Tildren® is supplied in a 30mL glass vial as a white, sterile lyophilized powder containing 500mg tiludronic acid (as tiludronate disodium) packaged in a folding carton. For technical assistance or to report suspected adverse reactions, call 1-888524-6332.

INFORMATION FOR OWNERS Prior to Tildren® administration, owners should be advised of the potential for adverse reactions in the hours or days following treatment. Adverse reactions within 4 hours post dosing may include signs of colic (manifested as pawing, stretching, getting up and down, sweating, rolling, looking at flanks, kicking at belly, frequent gas, and pacing). Owners should be instructed to contact their veterinarian immediately if any adverse reactions are observed. Owners should be advised to consult with their veterinarian prior to the administration of an NSAID following Tildren® administration.

Made in Canada Patent information: U.S. patent 6,057,306

TABLE 3. SYSTEMIC ANTIBIOTICS Medication Ceftiofur sodium (Naxcel®) (50 mg/ml)

Dosage, Route, Frequency

(broad spectrum); used in 1.1 to 2.2 mg/kg, IV or IM, Antibiotic equine reproduction for treatment of q 12h bacterial endometritis

3.0 mg ceftiofur equivaCeftiofur crystalline free acid (Excede®) (200 lents/kg, IM; retreat in 4 mg/ml) days if needed

Enrofloxacin (Baytril®) (50 or 100 mg/ml)

Indications

Antibiotic (broad spectrum); used in equine reproduction for systemic treatment of bacterial endometritis Antibiotic (broad spectrum); used in equine reproduction for treatment of bacterial endometritis, specifically for resistant Pseudomonas sp.; Note: intra-uterine therapy of the commercial product is associated with severe necrosis and is not recommended

5 mg/kg, IV, q 24 hours or 7.5 mg/kg, PO, q 24h

or greater than 60° of angulation to the vulva warrant perineal body reconstruction.

Following treatment, an ultrasound examination should be performed as the mare comes back into estrus for the presence of intrauterine fluid and confirming the uterine environment is free of infection by uterine culture and cytology during the next post treatment estrus.

Chronic Bacterial Endometritis Chronic cases of bacterial endometritis are those that have been treated traditionally as described for acute infections and are refractory to treatment. Current explanations as to why these cases are refractory to treatment are bacteria are protected by a biofilm from antibiotic exposure, antimicrobial resistance develops during treatment or the mare becomes re-infected with the same genus of bacteria. Due to these issues, the management of mares with chronic infections is often much more intense from both a diagnostic and therapeutic perspective.

An option for diagnosing these chronic infections includes a traditional guarded culture

TABLE 4. SUSCEPTIBILITY PATTERNS OF FUNGI TO ANTI-FUNGAL DRUGS COMMONLY USED TO TREAT FUNGAL ENDOMETRITIS IN MARES (FROM COUTINHO DA SILVA AND ALVARENGA, 2011).

Susceptibility pattern (% of isolates)

Anti-fungal Agent

Susceptible

Intermediate

Resistant

Polyenes Amphotericin B

96

0

4

Natamycin

100

0

0

Nystatin

100

0

0

Azoles Clotrimazole

80

13

7

Ketoconazole

81

15

4

Miconazole

43

41

16

Itraconazole

62

38

0

Fluconazole

44

14

42

Flurocytosin

83

0

17

swab and cytology brush; however, a more representative sample of the endometrium may be obtained from a small-volume lavage with culture or cytology of the centrifuged pellet. Endometrial biopsy for histopathology to evaluate the presence or absence of endometritis can be helpful when clinical and bacteriologic findings are inconclusive. Additionally, culture and cytology can be performed on the uterine biopsy sample and has been shown to be more diagnostic than traditional collection from a doubleguarded device.

While clients want to start treating these infections quickly, it is advantageous when developing a diagnostic plan to have the results of all diagnostics performed. The return of some diagnostic tests may take a few days to more than a week. Treatment plans should be focused on helping kill bacteria, disrupt a biofilm and remove debris from the uterine lumen. The treatment plan will start with a uterine lavage as described in acute endometritis. This will be followed up with an infusion of the most effective agent to kill and disrupt a preformed biofilm. Unfortunately, there is not an agent that is effective against all common genus of bacteria isolated from the equine uterus, and identification of the causative agent is warranted for the most efficacious treatment.

A series of in vitro studies were conducted to assess biofilm dispersal and/or bacterial killing for antibiotics and non-antibiotic agents alone or in combination against Gram-negative bacteria.

Our data indicates that antibiotics and non-antibiotic agents are more effective against biofilm if administered concurrently (i.e. in the same syringe). The table (Table 2) explains how to make up clinical treatments for local infusion into the uterus based on the in vitro data. The amount of either antibiotic or non-antibiotic agent for each infusion are the minimum effective concentrations against E. coli, K. pneumoniae and P. aeruginosa. The treatment period should be at least 72 hours in duration with repeated treatments every 24 hours (i.e. a uterine infusion of the selected combination once every 24 hours for three consecutive days). This treatment protocol resulted in complete biofilm dispersal and bacterial killing in vitro.

It is important to note that some non-antibiotic agents and antibiotics should not be combined in the same syringe. For example, the in vitro data indicated that mixing acetylcysteine with antibiotics in the same syringe resulted in reduced activity of the antibiotics.

We recommend antibiotic sensitivity testing for all Gram-negative organisms. Bacteria inherently resistant to an antibiotic will still be resistant when that antibiotic is used in combination with a non-antibiotic agent.

An additional consideration is that in many of these mares a 60 ml infusion of antibiotics results in several hundred mLs of fluid in the uterine lumen the next day. For these mares, we will often switch to systemic antibiotics if appropriate based on antimicrobial susceptibility TABLE 5. INTRAUTERINE MEDICATIONS USED IN THE TREATMENT (Table 3). A common antibiotic to use OF FUNGAL ENDOMETRITIS. systemically is Excede® to provide 10 Medication Dosage, Route, Frequency days of therapy.

Amphoteracin B (50 mg/ vial)

100 to 200 mg reconstituted in 50 to 100 mls sterile saline

Clotrimazole

500-700 mg in 50 to 100 mls sterile saline

Fluconazole (200 mg/ tablet)

100 to 250 mg in 50 to 100 mls sterile water; to reconstitute, add 5 mls DMSO to 1 gram (5 tablets) of fluconazole to dissolve; divide into 4 aliquots of 250 mg each; qs to 50 to 100 mls with sterile water

Lufenuron (Program®) (270 mg/packet)

540 mg in uterus suspended in 60 mls sterile saline, 270 mg applied to vaginal vault and clitoral area

Miconazole (1,200 mg insert)

1,200 mg insert deposited into uterus

Nystatin (100,000 IU/ gram; 30 gram vial)

5 grams suspended in 50 to 100 mls sterile water; or 0.5 to 2.5 million units

TABLE 6. SYSTEMIC MEDICATIONS THAT MAY BE USED IN THE TREATMENT OF FUNGAL ENDOMETRITIS. Medication

Dosage, Route, Frequency

Fluconazole (200 mg/ tablet)

14 mg/kg, PO, loading dose, followed by 5 mg/kg q 24h

Itraconazole (3 grams/ packet)

3 - 5 mg/kg PO q 24h for 2 to 3 weeks or longer

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FLORIDAAEP |

TREATMENT OF FUNGAL INFECTIONS Therapy for fungal endometritis involves treating the active infection via methods such as uterine lavage with dilute acetic acid or dilute povidone-iodine, plus systemic and/ or intrauterine infusion of anti-fungal agents in addition to correction of predisposing factors that could result in treatment failure. Administration of more than one anti-fungal agent may be indicated in refractory or recurrent clinical cases. Uterine lavage is indicated to remove retained fluid, reduce organism load, kill fungal organisms and remove biofilm. It may also be beneficial to apply topical anti-fungal medication to the vagina and clitoris as these areas may act as a reservoir or nidus for re-infection.

Ideally, selection of an anti-fungal agent would be based on results

@FLORIDA_VMA | The Practitioner 25

TABLE 7. UTERINE LAVAGE THERAPIES THAT MAY BE USED IN THE TREATMENT OF FUNGAL ENDOMETRITIS. Medication

Dosage, Route, Frequency

N-Acetylcysteine solution (20 %) (200 mg/ml)

30 mls (6 grams) diluted into 150 mls sterile saline infused into uterus

Dimethyl sulfoxide (DMSO) (99%)

50 ml DMSO per liter saline; may repeat as needed; follow with lavage with 1 liter saline or LRS

Hydrogen Peroxide (3 %)

60 to 120 mls infused into uterus; follow the next day with lavage using sterile saline or lactated Ringer’s solution (LRS)

Lactated Ringer’s Solution (LRS)

1 to 4+ liters; repeat lavage until effluent fluid is clear

Povidone-Iodine (Betadine® Solution) (1 %)

10 -15 mls added to 1 liter sterile saline

Saline (0.9 %)

1 to 4+ liters; repeat lavage until effluent fluid is clear

Tris-EDTA (Tricide®)

250 to 500 mls infused into uterus; followed by uterine lavage with lactated Ringer’s solution (LRS)

Acetic Acid (Distilled White Vinegar) (2 %)

20 – 100 mls added to 1 liter sterile saline

of susceptibility tests for each case of fungal endometritis.

Unfortunately, anti-fungal susceptibility tests are not performed in many diagnostic laboratories and several weeks are often required from sample submission to when results are obtained. Clinicians often rely on empirical choices for initial anti-fungal therapy drugs based on published susceptibility patterns while awaiting organism identification and susceptibility testing (Table 4).

Several anti-fungal agents are available for intra-uterine therapy (Table 5). Fluconazole and itraconazole are reported to be absorbed following oral administration, with fluconazole being the most cost effective therapy in the horse. Oral administration of an anti-fungal agent can provide long-term, anti-mycotic activity and may be an important component of a multifaceted treatment program for fungal endometritis. Lufenuron has also been reported to be an effective treatment against fungal endometritis by inhibiting chitin synthesis in the cell wall. Lufenuron may not be effective in all cases as not all fungal organisms have chitin in their cell walls.

Tables 5, 6 and 7 list systemic medications and uterine therapies used in the treatment of fungal endometritis.

Mares are often treated empirically while awaiting results of antifungal susceptibility tests. A combination of two anti-fungal agents may be warranted in the event that the fungal organism is resistant to one of the agents. A potential protocol for treatment of a mare with fungal endometritis is presented below:

nystatin (500,000 IU in 50 mls saline, IU q 24h x five days) or one miconazole pod (1,200 mg IU, once) as indicated by organism and antimicrobial sensitivity tests.

4. Lavage uterus (± oxytocin) at conclusion of intrauterine therapy.

5. Short-cycle mare with prostaglandins.

6. Re-culture when back in estrus.

7. Anticipate treatment for secondary bacterial infection (esp.

S. equi subsp. zooepidemicus).

It is common for a moderate to heavy growth of a bacterial organism, such as Streptococcus equi subsp. Zooepidemicus, to be detected in mares following treatment of fungal endometritis.

Consequently, it is often necessary to treat for bacterial endometritis along with or after treatment for fungal endometritis.

CONCLUSION Treatment of infectious endometritis due to latent bacteria, biofilm or fungal organisms can be difficult; however, an understanding of the pathophysiology of the organisms in their current states can help when selecting treatment protocols.

References:

1. Uterine lavage during early estrus with sterile saline (plus acetic acid or other agent) and administer oxytocin (20 units, IM or IV) to promote evacuation of uterine fluid. May be repeated daily as needed.

1.

2. Administer systemic fluconazole therapy (14 mg/kg loading dose PO, once, followed by 5 mg/kg maintenance dose PO q 24h for two to three weeks).

2. Coutinho da Silva MM and Alvarenga MA. Fungal endometritis. In Equine Reproduction, eds McKinnon AO, Squires EL, Vaala WE, Varner DD. Wiley-Blackwell 2011;2643-2651.

3. Administer intrauterine anti-fungal therapy using either

Christoffersen M, Söderlind M, Rudefalk SR, Pedersen HG, Allen J, Krekeler N. Risk factors associated with uterine fluid after breeding caused by Streptococcus zooepidemicus.

Theriogenology. 2015;84:1283-1290.

3. Ferris RA, McCue PM, Borlee GI, Loncar KD, Hennet ML, Borlee BR. In Vitro Efficacy of Nonantibiotic Treatments

26 The Practitioner Issue 4 • 2018

on Biofilm Disruption of Gram-Negative Pathogens and an In Vivo Model of Infectious Endometritis Utilizing Isolates from the Equine Uterus. J Clin Microbiol. 2016;54:631–9.

4.

Petersen MR, Skive B, Christoffersen M, Lu K, Nielsen JM, Troedsson MHT, et al. Activation of persistent Streptococcus equi subspecies zooepidemicus in mares with subclinical endometritis. Vet Microbiol. 2015;179:119–25.

5. Dascanio, J. J. (2011). How and When to Treat Endometritis With Systemic or Local Antibiotics, AAEP Proceedings,57, 24-31.

6. Ferris, R. A. (2014). Bacterial endometritis: a focus on biofilms. Clinical Theriogenology, 6, 315–319.

7. Gores-Lindholm, A. R., LeBlanc, M. M., Causey, R., Hitchborn, A., Fayrer-Hosken, R. A., Kruger, M., et al.

(2013). Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance. Theriogenology, 80, 218–227.

8. LeBlanc, M. M. (2010). Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare. Reproduction in Domestic Animals, 45 Suppl 2, 21–27.

9. LeBlanc, M. M., & Causey, R. C. (2009). Clinical and subclinical endometritis in the mare: both threats to fertility.

Reproduction in Domestic Animals, 44 Suppl 3(s3), 10–22.

800.824.3703

Ryan A. Ferris DVM, MS, DACT Owner, Summit Equine, Inc. Newberg Oregon Dr. Ferris graduated from veterinary school at Washington State University in 2007. He completed an internship in equine surgery, medicine and reproduction at the Equine Medical Center of Ocala in 2008, followed by a residency in equine reproduction at Colorado State University. He received a MS in clinical science from Colorado State University, passed the board examinations for the College of Theriogenologists and was an assistant professor at Colorado State University from 2010-2017. In 2018, Dr. Ferris and his family moved to Newberg, Oregon and established Summit Equine, Inc. Summit Equine is a referral equine reproduction practice for mares and stallions. They offer services in breeding management (fresh, cooled or frozen); embryo transfer; problem mares; oocyte aspiration; stallion collections for fresh, cooled or frozen semen; international shipment of semen; and stallion evaluations. Interests: Bacterial and fungal endometritis, biofilm, post mating-induced endometritis, and embryo transfer.

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FLORIDAAEP |

@FLORIDA_VMA | The Practitioner 27

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28 The Practitioner

Issue 4 • 2018

Winning in their blood.

in their joints. · High viscosity solution of Hyaluronic Acid, Chondroitin and Glucosamine · Veterinarian trusted since 2006 · Patented formulation For more information, visit www.bimedaequine.com or call 1-888-524-6332.

Veterinary Use Only. Patent Nos.: 6,979,679 / 7,485,629 / 8,455,458. CAUTION: This device is restricted to use by or on the order of a licensed veterinarian. WARNING: Do not administer to animals that are to be slaughtered for use in food. Keep out of reach of children. *Polyglycan® is a registered trademark of Bimeda, Inc. All rights reserved. © 2018 Bimeda, Inc.

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@FLORIDA_VMA | The Practitioner 29

the secret is out!

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30 The Practitioner

Issue 4 • 2018

FORUM

2019

Tildren

®

(tiludronate disodium)

Bisphosphonate drug for intravenous infusion

Turning heartache into hope.

Providing lasting relief for your horse with Navicular syndrome.

Effective

Long-lasting

Safe

Control clinical signs

To learn more about Tildren®, ask your Veterinarian or visit tildren.us. *CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use in horses with impaired renal function or with a history of renal disease. NSAIDs should not be used concurrently with Tildren®. Concurrent use of NSAIDs with Tildren® may increase the risk of renal toxicity and acute renal failure. The safe use of Tildren® has not been evaluated in horses less than 4 years of age, in pregnant or lactating mares, or in breeding horses. Tildren® is a registered trademark of Bimeda Animal Health Limited. All rights reserved.

Global Excellence in Animal Health