2016 FALL: Xylitol Toxicity | Rehabilitation | Current Heartworm Disease Topics | Ophthalmic Emergencies | Meet Dr. Josh Bruce
Xylitol Toxicity: Not Just Gum
The number of dogs presenting for xylitol ingestion and toxicity has increased dramatically over the past few years. Xylitol is a crystalline sugar alcohol used as a sugar substitute sweetener in many products including sugar-free gum, candy, chewable vitamins, nutritional supplements and baked goods. It is available in a granulated form for baking. Based on demonstration of anti-cariogenic properties, xylitol is added to toothpastes and other oral hygiene products. In a retrospective evaluation of 192 cases of xylitol ingestion, 96% of the dogs presented for ingestion of sugar-free gum.1
Xylitol has a wide margin of safety in people but is extremely toxic to dogs. Compared to humans, dogs experience a rapid and severe increase in blood insulin resulting in profound hypoglycemia which can last up to 24 hours. Similar effects are seen in cows, goats and rabbits. Cats and ferrets have not shown toxic effects. Ingestion of large amounts of xylitol has resulted in liver failure in dogs.
Diagnosis of xylitol toxicity is based on history of ingestion, symptoms and bloodwork. Common presenting clinical signs include vomiting, lethargy and weakness. Diarrhea, collapse and seizures may be seen. Hypoglycemia has been reported within 30 minutes of ingestion but can occur up to 12 hours post-ingestion.
Treatment recommendations are based on the amount of xylitol ingested (see table below). There is no known antidote and a narrow window for safe decontamination. Xylitol is rapidly absorbed with peak plasma concentrations at 30 minutes. Emesis is recommended in asymptomatic dogs. Activated charcoal is not likely to be beneficial as charcoal does not bind to alcohol-type compounds.
Calculating the amount of xylitol contained in products can be difficult. Products that list xylitol as the first ingredient tend to be the most toxic. The amount of xylitol in gum can range from 0.9 mg to 1000 mg/piece. While some gum products specify the xylitol content on the label, many manufactures consider this to be proprietary information. The ASPCA Animal Poison Control Center (ASPCA APCC) recommends that if xylitol is the first sugar alcohol in the ingredient list, then the estimated dose should be based on the total amount of sugar alcohols. If not the first ingredient, xylitol should be estimated to be 0.3gram/piece of gum. Granulated (baking) xylitol contains 190 grams/cup. Gabapentin liquid contains 300 mg xylitol/ml and could reach toxic levels at higher doses.
The ASPCA APCC recommends that dogs ingesting 50-100 mg/kg should receive decontamination and monitoring.2 However, hypoglycemia has been reported in a dog ingesting an estimated 30 mg/kg xylitol dose.1 Dogs ingesting >100 mg/kg are at increased risk for hypoglycemia and should be treated more aggressively. Ingestion of higher doses increases the risk of liver failure and coagulopathy. All dogs reported developing xylitol induced liver failure ingested > 500 mg/kg; however, it is not clear at this time whether the effect is dose-related or idiosyncratic. In a case report of dogs developing acute liver failure subsequent to large dose xylitol exposure, six of the eight dogs did not develop hypoglycemia prior to the onset of liver failure.3
The prognosis is very good for dogs treated promptly and for dogs with uncomplicated hypoglycemia. In a 2015 retrospective study reporting 192 cases of xylitol ingestion, 15.6 % developed hypoglycemia and 21.9 % of dogs with serum biochemistry panels performed developed mildly increased ALT or total bilirubin. No dogs developed clinical signs or biochemistry values consistent with liver failure. All dogs survived. Mild increases in liver enzymes usually resolve within a few days with supportive care.
Severe or progressive increases in liver enzyme activities (>1000), hyperbilirubinemia and coagulopathy, carry a more guarded prognosis. Mortality rate of 70-80% is reported when acute liver failure develops. Hyperphosphatemia appears to be a poor prognostic indicator. At BluePearl, we have treated several dogs with severe liver failure and coagulopathy secondary to xylitol ingestion. Although we have not been able to save all of them, we have gotten a good number home after treatment with fresh frozen plasma, fluids, GI protectants and liver protectants. In one case in which the dog ate two cups of baking xylitol, the dog developed active bleeding due to coagulopathy and ALT went up to 50,000. However, after several plasma transfusions, the dog was able to go home and bloodwork was completely normal 8 weeks later.
|Ingested Dose||Treatment recommendation|
|50-100 mg/kg||Induce vomiting if asymptomatic, observe|
|100-500 mg/kg||Induce vomiting if asymptomatic. Obtain baseline glucose, potassium, phosphorus, biliruibin and liver enzymes. Monitor blood glucose every 1-2 hours for at least 12 hours and other tests every 24 hours for at least 72 hours. If hypoglycemia develops, 1-2 ml/kg bolus of 25% dextrose and continue fluids supplemented with 2.5-5% dextrose to maintain normal glucose. Continue until glucose concentration can be maintained without supplemental dextrose.|
|>500 mg/kg||As above, except administer supplemental dextrose despite normal BG. Add liver protectants (N-acetylcysteine or Denamarin)|
Article courtesy of our colleague from BluePearl in Washington, Linda Barton, DVM, DACVECC.
- Dunayer EK. New findings on the effects of xylitol ingestion in dogs. Veterinary Medicine 2006; 791-797.
- DuHadway MR, Sharp CR, Meyes KE, et al. Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007-2012) JVECCS 25(5) 646-654.
- Dunayer EK. Gwaltney-Brant SM. Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs. Journal American Veterinary Medical Association 2006; 229, 1113-1117.
Better Than Performance-Enhancing Drugs
If you have ever suffered an orthopedic, muscular or neurologic injury, you know how valuable physical rehabilitation can be to your recovery. Even short periods of limited use, or disuse, can restrict the function of an affected limb, or worse, lead to chronic intermittent or persistent pain. Physicians prescribe physical therapy for people with joint injuries, back problems, tendonitis, ruptured cruciate ligaments and rotator cuff problems. The sooner a person begins therapy to recover the health of injured tissues, the more complete the recovery and the better the person feels.
Dogs are no different than humans when it comes to joint, muscle and neurologic injuries. The quality of our patients’ lives can be severely limited as a result of an incomplete recovery from even simple injuries. Arthritis can also result with a rapid deterioration in a pet’s activity level. Frequently, the inactivity and discomfort associated with an injury or arthritis is reversible. We have all seen the benefit that anti-inflammatory medications can have on our patient’s activity.
But pain relief is not the only ingredient for recovery in injured and arthritic pets. Maintaining the health of the joints, peri-articular tissues and supporting muscles is also necessary to ensure that our patients can support the weight and stress they place on their bodies.
An animal physical therapist can be a tremendous help to clients who want to give their pets the best opportunity to completely recover from an injury or remain active in the face of progressive arthritis. Range of motion activities, controlled exercises and time spent in an underwater treadmill are all designed to help pets recover their strength and regain their mobility. When we don’t recommend physical rehabilitation to our clients, they potentially miss an opportunity to keep their pets vibrant, active and pain free.
Physical rehabilitation is not just for humans. If you have a patient who might benefit from physical therapy, please call Ruth Schmitchen, DVM, CVA, CCRP, with our rehabilitation service at 502.244.3036.
As the Worm Turns: Current Heartworm Disease Topics
The American Heartworm Society (AHS) was founded in 1974 by a group of veterinarians and scientists with the mission of leading the veterinary profession and public in understanding heartworm disease (HWD). The AHS participates in funded heartworm (HW) research and provides easily accessible expert guidelines detailing current information on effective procedures for the diagnosis, treatment and prevention of heartworm disease. The AHS is now considered the leading expert source on HWD, a topic on which our knowledge is constantly expanding. Renewed emphasis on the importance of heartworm prevention and new information about heartworm resistance, testing and treatment prompted the AHS to revise its guidelines for dogs and cats in 2014. This article will discuss some of the topics of concern associated with the AHS guideline changes.
What about reports of heartworm resistance to the available macrocyclic lactones preventatives?
Resistance, or lack of efficacy (LOE), of a HW preventative is defined as a dog testing HW positive despite appropriate dosing and consistent monthly administration of the preventative. The majority of cases of suspected resistance to HW preventatives can be explained by owner compliance issues; either failure to administer an adequate dose or failure to administer the preventative on time. This fact has been confirmed by retrospective epidemiologic studies that evaluated dogs receiving HW preventatives with subsequent infection, including a review of the owners’ purchase pattern of the preventatives. An animal can become infected with HW by missing or delaying administration of just one dose of preventative, especially in endemic areas. If a dog on preventative therapy becomes positive for HW, it is important to question owners about appropriate administration of the preventative as well as review their preventative purchase record.
A few microfilariae strains have been identified that tolerate high doses of the macrolide preventatives. Six resistant strains have been identified with research in the past 10 years. When the L3 larvae of these microfilariae were injected into dogs they matured to adult HWs despite appropriate administration of preventative doses of the macrocyclic lactones. Resistance of these specific microfilariae strains was found with all tested products: ivermectin, milbemycin, selamectin and moxidectin injectable. The majority of resistant isolates have been identified from the Mississippi River Valley region where the majority of LOE has been reported. The extent and degree of spread of these isolates to other regions is not clearly documented. There is some concern for these isolates traveling northward, even to Canada, with the transport of rescued dogs following Hurricane Katrina. The mechanisms for microfilarial resistance are not understood and are the subject of ongoing genetic research.
Other possible reasons for LOE of HW preventative therapy include failure of attempted administration (dog spits pill out), failure of absorption of the active ingredient (GI malabsorption), biologic variation in dog’s drug metabolism, and the dog’s immune system parasite response. Failure of owner compliance remains the most consistent factor in preventative failure. The currently available preventatives are highly effective when administered per manufacturers’ recommendations with year round administration. To minimize risk of preventative failure, the veterinary practice team must educate clients regarding implications of HW infection, risk of HW in their area, and ensure that their pets are receiving appropriate preventative dosing.
What are Wolbachia and how are they involved in HWD?
Wolbachia are symbiotic gram-negative intracellular bacteria related to other rickettsial organisms. They are found in the reproductive tract of adult HW and in all stages of microfilariae. Wolbachia are necessary for all stages of dirofilariae to mature, thrive, reproduce and maintain infectivity. The pathogenesis of HWD is suspected partially related to vascular immune response to a surface protein produced by Wolbachia resulting in pulmonary and renal vasculitis. Wolbachia, like other rickettsial organisms, are susceptible to doxycycline. Use of doxycycline in conjunction with adulticide therapy is recommended to remove or reduce the number of Wolbachia from HW adults and microfilariae. Potential benefits of Wolbachia removal include reduced ability of HW adults to reproduce, reduced infectivity of microfilariae if ingested by mosquitos, inability of adults and microfilariae to thrive leading to deterioration and death, and reduction of host lung and kidney pathology by reducing reaction to Wolbachia surface protein and adult worm death. Higher dosing of doxycycline is now recommended for HWD treatment at 10 mg/kg q 12 hours for 30 days with ivermectin prior to initiation of immiticide therapy.
What about the slow-kill protocol?
Monthly treatment of dogs with preventative doses of ivermectin was found in studies to shorten life span of adult HW to two to three years instead of three to seven years. Ivermectin is the only macrocyclic lactone that has shown efficacy as an adulticide. Studies with milbemycin, selamectin and injectable moxidectin have not shown effect on adult worm survival. Subsequent studies found that doxycycline added to ivermectin therapy may shorten adult HW survival time to 9 to 24 months. These studies were the basis of the slow-kill protocol. While initially considered an alternative therapy to immiticide management, other studies have shown that dogs managed with slow-kill therapy continue to develop severe pulmonary pathology that may progress to pulmonary hypertension and heart failure. Damage to the pulmonary vasculature occurs due to pneumonitis and pulmonary vasculitis caused by the host immune response to the persistent presence of live and dying adult worms. Another concern for the slow-kill protocol is possible development of ivermectin resistance by adult HW and microfilariae that may be produced during the initial months of therapy. This could result in ivermectin resistant strains of microfilariae that may infect feeding mosquitos.
The AHS no longer recommends use of the slow-kill protocol due to risk to the patient and concern for development of ivermectin resistance. Slow-kill protocol should only be considered in patients with other significant medical illness where immiticide is contraindicated or for clients with financial hardship.
A visit to the American Heartworm Society website can provide more detail about these and other topics related to HWD.
We would like to thank our colleague from BluePearl in Illinois, Susan E. Yohn, DVM, DACVIM, DABVP, for allowing us to use this article for Companion.
A Sight for Sore Eyes: Ophthalmic Emergencies
Proptosis, “eye out of the socket,” is the forward displacement of the globe out of the orbit with subsequent entrapment of the eyelids behind the eye. It occurs due to trauma to the head, usually a dog fight. Dogs with wide eyes and shallow orbits are at higher risk. Cats and long-nosed dogs require very severe trauma for the eye to proptose.
Factors to consider before replacing the eye into the orbit:
- Time elapsed since injury
- How many extraocular muscles are ruptured (no more than three)
- Presence of hyphema
- Whether or not the the globe is soft
Because more than three extraocular muscles are ruptured, compromising the globe arterial supply, this eye must be enucleated.
If the decision is made to replace the globe in the orbit, it should be done immediately. The patient should be stable enough for a short period of general anesthesia. After the area is prepped (recommend minimal clipping, trim long hairs with scissors and use betadine solution 1:50 dilution only – betadine scrub and chlorhexidine should never be used near the globe), infiltrate the lateral canthus with local anesthesia, then perform a lateral canthotomy if needed. Depending on the size of the palpebral fissure, lateral canthotomy may not be required. This will enlarge the palpebral fissure immediately and allow grasping of the skin on the upper and lower eyelids with Allis forceps; pull gently up and over the globe. Once the eyelids are manipulated over the globe, the eye returns to the orbit. Suture the lateral canthotomy and place a temporary tarsorrhaphy to protect the globe during the first two weeks postsurgery. Topical antibiotic, oral analgesia and anti-inflammatories are in order.
Postoperative deviation of the globe occurs due to rupture of extraocular muscles. Strabismus often diminishes over weeks to months.
Glaucoma, increased pressure within the eye beyond that compatible with normal ocular function, vision and comfort, is one of the leading causes of blindness in animals and people. It is caused by a disturbance in the flow of fluid within and out of the globe. Once one eye has been affected by primary glaucoma, the second eye will normally be affected within two years. Other causes of glaucoma include inflammation, trauma and intraocular tumors. Glaucoma patients often present with a painful eye and decreased vision. Other presenting complaints include injected conjunctival and episcleral vessels, gray uneven discoloration of the cornea, mid-range mydriatic pupil and elevated intraocular pressure. Glaucoma is one of the ophthalmic conditions with severe visual implications and should be referred to a veterinary ophthalmologist for further management. It is rarely cured, and many animals lose vision despite medical and surgical treatment.
An accurate diagnosis of glaucoma is based on a thorough ocular examination and measurement of the intraocular pressure (IOP) with a tonometer. Normal IOP should be lower than 20-25 mmHg. Acute glaucoma is an ophthalmic emergency and must be treated immediately! If the pressure remains elevated for a few hours, permanent vision loss occurs. The combination of the carbonic anhydrase inhibitor, dorzolamide, and a beta blocker, timolol, works very well together with the prostaglandin analogue, latanoprost.
Lens luxation into the anterior chamber may be seen with elevated intraocular pressure or not. It is a true ophthalmic emergency that requires surgery. Prompt surgical removal of the luxated lens is recommended if prognosis for vision is good.
The normal lens position is behind the pupil. When luxation occurs the lens may be displaced completely in front of the pupil (anterior luxation) or behind the pupil to the back of the eye (posterior luxation). The luxation can also be partial (incomplete or subluxation). Lens luxation is observed in young adult dogs usually 4 – 5 years of age. Primary lens luxation is common in terrier breeds such as the wirehaired fox terrier, Jack Russell terrier, Sealyham terrier, Tibetan terrier and terrier crosses. The breeds predisposed to this condition are border collie, Australian blue heeler, German shepherd dog and Shar Pei. Primary lens luxation is bilateral, although the onset of luxation varies between the eyes. Secondary lens luxation and subluxation may occur after the globe has increased in size (buphthalmia) in glaucoma cases or after chronic intraocular inflammation (uveitis, cataracts).
Superficial corneal ulcer. Notice the positive fluorescein uptake on the stroma and between the stroma and the epithelium at the ulcer margin.
A deep corneal ulcer, descemetocele, progressed from a superficial ulcer.
Anterior lens luxation usually manifests with acute tearing (epiphora) and eye pain and redness. Cloudiness of the cornea is present if the intraocular pressure is elevated (glaucoma). If the cornea is clear, the luxated lens can be observed in front of the pupil. The luxated lens can migrate back and forth through the pupil.
Corneal ulcers start as simple superficial ulcers that become deeper. One should be worried if the ulcer is deep (descemetocele) and there is a risk of rupturing. Topical antibiotics and pain management, topical atropine, oral analgesics and anti-inflammatories, are recommended. Use of an E-collar is also recommended. An uncomplicated ulcer should heal within 7 to 10 days. If healing takes longer, the ulcer may be indolent and require debridement and grid keratotomy.
Corneal abscesses occur when a corneal ulcer becomes infiltrated by bacteria. The corneal stroma may be greenish yellow and become malacic or gelatinous. Bacteria such as P. aeruginosa and S. betahemolyticus are involved in progression of the ulcer. Clinical signs of a stromal abscess include increased tearing, severe ocular pain, redness and evidence of a whitish to yellow discoloration of the cornea.
A stromal abscess is an ocular emergency, although it may not require immediate intervention by an ophthalmologist. You can stabilize the eye by establishing strong, frequent (every 2 hours) topical antibiotic therapy (quinolones), anticollagenases (serum, EDTA), systemic antibiotics (Clavamox® or Unasyn®) and analgesia. It is often necessary to admit these patients for 24 hours. Surgical repair of the cornea (conjunctival flap) may be necessary if the ulcer progresses to deep layers, and the eye is at risk of perforation or has already perforated.
Infected anterior stromal corneal ulcer with collagenolysis
Uveitis occurs when the uveal tract, rich in vascularization, becomes inflamed. Protein, red and white blood cells leak to the usually transparent intraocular fluid, making it turbid. The condition may be present in one or both eyes. Bilateral involvement is seen more frequently in patients with infectious, parasitic, neoplastic or autoimmune diseases.
There are many causes of uveitis; it is frequently considered an ocular manifestation of a systemic disease. Among the causes are trauma, cataract formation, infections and tumors. Some of the infections in dogs include Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, anaplasmosis, infected uterus, viral hepatitis and systemic fungal infections. In cats the causes include feline leukemia virus (FeLV), feline immune deficiency virus (FIV), feline infectious peritonitis (FIP), toxoplasmosis and bartonellosis.
Symptoms of uveitis include eye pain, squinting, redness, tearing, elevation of the third eyelid, cloudiness of the cornea and a small pupil. On occasions there is pus or blood inside the eye.
Diagnosis of uveitis requires a complete systemic workup to include blood and urine testing and thorax and abdomen imaging; however, approximately 60% of the cases are a diagnosis of exclusion. Possible sequela include attachment of the pupillary opening to the lens capsule (posterior synechiae) which can result in abnormal pupil shape (dyscoria), secondary glaucoma (high intraocular pressure), secondary cataract formation and retinal detachment. The eye may become blind and painful in which case surgical removal (enucleation) will be recommended. Emergency treatment should include topical eye medication to control intraocular inflammation, analgesia, systemic anti-inflammatories and antibiotics, and possibly medications to prevent glaucoma. If there are no corneal ulcers prednisolone acetate and atropine are recommended.
For support with ophthalmic emergencies or questions, please contact our ophthalmology service at 502.244.3036.
Article courtesy of our colleague from BluePearl in Massachusetts, Clara Williams, DVM, DACVO.
Meet Dr. Josh Bruce
“My interest in veterinary surgery can be traced back to veterinary school and the cultivation by an amazing orthopedic surgery mentor,” said Joshua Bruce, DVM. “As a third year veterinary student at Auburn University, Dr. Ron Montgomery made orthopedics fun and turned my trajectory from general practice into the surgery specialty.”
Dr. Josh Bruce,Surgery Service
After graduating from Auburn University’s College of Veterinary Medicine, Dr. Bruce completed a one-year internship at Georgia Veterinary Specialists in Atlanta (now a BluePearl hospital) followed by a surgical internship at BluePearl Veterinary Partners in Overland Park, Kansas. He completed his residency at BluePearl Veterinary Partners in Southfield, Michigan, and has now returned home to Kentucky to join our surgery service.
What aspects of surgery do you enjoy the most?
Even though my initial interest was orthopedic surgery, as my training progressed, I began to appreciate the art of soft tissue and neurologic surgery. I can honestly say that I enjoy all three aspects of veterinary surgery equally. Some of my favorite procedures include management of chylothorax, correction of angular limb deformities and fracture fixation.
What keeps you interested in cases day after day?
I thoroughly enjoy educating clients on the aspects of the disease that is affecting their four-legged family member. The more educated a client is about the disease, the better prepared they will be to make the best decision for their family. This education allows me to interact with different people every day and provides different nuances to every case.
What was one of the most interesting cases that you saw in your residency?
That is a tough question! I saw so many interesting cases. A particular case comes to mind – a small mixed breed dog with an aggressive soft tissue sarcoma over the greater trochanter. A simple amputation would not allow large enough margins around the mass. We were able to not only amputate the limb, but we removed a portion of the pelvis on that side. This dog recovered uneventfully, and we were able to obtain a surgical cure for this pet. The owners were ecstatic! Being able to take an owner from despair to jubilation with our work is a true gift!
Why did you choose to move to Louisville?
My wife and I have been counting down the days until we could move back to Kentucky. This is the state where we both grew up. We both attended Western Kentucky University for undergraduate studies. Currently, her family is in Northern Kentucky, and mine is in Nashville. Louisville provides the perfect midway point between our families. Plus, you can often find us exploring new restaurants, and Louisville is quickly becoming a “foodie destination.” We are both looking forward to settling down and making Louisville our home for many years.