2016 FALL: Xylitol Toxicity | Deciphering Bronchial Lung Patterns| Ophthalmic Emergencies | Palliative Radiation | Clinical Trial: Anemic Cats with Lymphoma
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.
BluePearl Clearwater and Tampa have critical care specialists available seven days a week who are happy to take your most difficult and critical cases.
|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.
Deciphering Bronchial Patterns
Whether you are relatively new to looking at digital radiographs or not, the amount of “background” pattern in the lungs can often be misleading. The interstitium is actually visible on a normal radiograph especially in the caudodorsal lung fields on the lateral projection because of the large size of the lobes and larger amount of superimposed structures.
The interstitium appears as the lacy soft tissue opacity between airways and vessels and is more prominent in expiratory images. This opacity, however, should not blur margins of the vessels, and as long as the pulmonary vessels are distinctly visible, you can infer that lung parenchyma is adequately aerated and normal. On top of this background opacity, the walls of the primary bronchi should be visible in a normal patient as opaque double parallel lines leaving the trachea up to the level of the second divisions. Visible bronchial walls should stay thin, linear, and distinct without blurring opacity in the immediate peribronchial parenchyma (Figure 1).
Figure 1. Normal canine thorax (a) in which vessel margins and background interstitium are distinctly visible. In the close-up of the hilar region (b), note only the walls of the primary bronchi are visible (white arrows).
Yes, you WILL see airway walls near the hilus of the lungs in a normal dog, but you should not be able to follow these airways out into the periphery. The hallmark of a bronchial pattern is visualizing airway walls as double parallel lines (side-view, “tram tracks”) or rings (end-on-view, “doughnuts”) in the pulmonary periphery. The best places to look in the pulmonary periphery on the lateral projection are superimposed with and just cranial to the cardiac silhouette, overlying the diaphragm, and just ventral to the vertebral bodies. On the ventrodorsal projection, look lateral to the cardiac silhouette, and overlying the diaphragm caudally. Try to avoid the central hilar portions of the lung fields as these will always look “busy.” The thickening of and excess of visible airway walls in a pathologic state causes the lung fields to overall appear linear and “streaky” (Figure 2). This is a common finding in geriatric patients due to fibrosis from aging or prior disease. Bronchial patterns are typically diffuse in distribution.
Figure 2. Lateral thoracic radiograph of a 1-year-old border collie who presented for coughing, sneezing, oculonasal discharge and fever, diagnosed with infectious tracheobronchitis. Note thickened/fuzzy and prominent airway walls in the pulmonary periphery (white arrows = “tram tracks”, white circles = “doughnuts”).
One of the reasons bronchial patterns are often difficult to distinguish is that the abnormal opacity will not be as noticeable adjacent to surrounding interstitium. However, as with many things in radiology lung patterns are not always black and white (pun intended), and mixed patterns such as bronchial and interstitial or intertial and alveolar may exist with certain disease processes. Caution must be taken to ensure an artefactual change is not to blame (i.e. underexposure or an expiratory image causing the appearance of unstructured interstitial opacity).
What does it mean?
Cellular infiltrate from primary airway disease causing wall thickening is often the cause of increased conspicuity and a bronchial pattern on radiographs, but a bronchial pattern may also result from wall mineralization, luminal exudate, thickened bronchial mucosa or peribronchial cuffing (i.e peribronchial interstitial pattern). Depending on the type and stage of the particular disease process, other pulmonary patterns may be concurrently present.
Here is a list of canine/feline differentials to consider – note some of these may be disregarded due to lack of certain endemic infectious diseases here in Florida, but travel history must be considered. Further characterization of airway disease may be obtained with airway sampling (i.e. bronchoalveolar lavage or tracheal wash) with cytology and culture, and in some cases thoracic computed tomography is helpful in better evaluating distribution and severity of disease.
If you are interested in submitting radiographs for our radiologists to review, please contact our radiology service in our Tampa hospital at 813.933.8944 or at email@example.com
Differentials for a bronchial pattern
- Allergic bronchitis – asthma
- Infectious bronchitis
- Paragonimus kellicoti (lung fluke) – dogs and cats, often with cystic lesions
- Alurostrongylus abstrusus (lungworm) – cats, often with patchy interstitial and alveolar patterns
- Heartworm – often with interstitial pattern, enlarged pulmonary arteries, and right-sided cardiomegaly
- Fungal – Histoplasmosis in cats. Other types often have pulmonary nodules and lymphadenopathy (e.g. caccidiomycosis—this occurs in neighboring states such as Arizona and California)
- Neospora caninum – dogs
- Toxoplasma gondii – cats, often with regions of patchy consolidation
- Other inflammatory bronchitis
- Toxic/inhaled irritant – i.e. smoke inhalation
- Acute lung injury/acute respiratory distress syndrome
- Cushing’s disease, hypercalcemia, hyperparathyroidism – bronchial wall mineralization mimicking a bronchial pattern
- Bronchogenic carcinoma, although often associated with mass lesions
- Pulmonary edema (an interstitial pattern that starts out as peri-bronchial with mild or early disease) – possible manifestation of cats and dogs in congestive heart failure
Article courtesy of our colleague from BluePearl in Washington, Ellie Nuth, DVM, DACVR.
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.
We see ophthalmology cases at all four of our Florida hospitals. Drs. Miller, Stine and Welihozkiy are happy to take your phone consults and transfers.
Article courtesy of our colleague from BluePearl in Massachusetts, Clara Williams, DVM, DACVO.
Palliative Radiation – New Uses Are Not So Palliative
Palliative radiation has traditionally been used to treat clinical problems or signs, such as bone pain, difficulty eating from oral masses or obstruction of an organ such as the colon, esophagus or trachea. It was not really thought of as a primary treatment for any tumor. However, in recent years this mindset has been changing in veterinary medicine. Many pet owners, whose pets have cancer, choose not to pursue definitive radiation due to time commitments, concerns about daily anesthesia, severe side effects or cost. Palliative radiation is usually administered in one to six treatments, over a three-week period. Most pets have few to no side effects from the treatment, and the risk of anesthesia complications is quite low. Because of this, palliative radiation is often used in animals. However, in recent years we have begun to learn that palliative treatment protocols, or ones that we thought were palliative, may actually play a role in controlling tumors in some situations.
- Injection site sarcomas – Recent studies have shown these types of radiation protocols can help slow recurrence in cats with injection site sarcomas. Cats treated with surgery followed by four radiation treatments had control of their tumor for approximately 2½ years. (Eckstein et al Vet Compar Oncol 2009)
- Nasal tumors in dogs are often difficult to treat because definitive treatment can result in severe local side effects, during radiation therapy. However, palliative radiation has resulted in survival times of 11 months in one study. (Cancedda et al Vet Radiol Ultrasound 2015). This type of response gives a nice alternative for pet owners who can’t pursue definitive treatment.
- Soft tissue sarcomas in dogs can also be treated with a palliative course of treatment. In these cases, either treatment of the tumor alone or treatment after an incomplete excision can result in survival times of well over a year. (Cancedda et al Vet Radiol Ultrasound 2015, Kung et al Vet Compar Oncol 2014)
- Brain tumors can also be treated with more palliative protocols. One study has shown that pituitary tumors can be fairly well controlled with a limited number of treatments. (Marcinowska et al Vet Radiol Ultrasound, 2015)
These, and other studies are changing the way that we approach treatment of tumors in dogs and cats. Animals that we would have given up on in the recent past, can now be treated with a reasonable chance to get control of their tumors. With a limited number of treatments, fewer anesthesia episodes and limited side effects, palliative treatment may be an option for many pets with cancer.
Drs. Coyle and Kane, from our oncology service, see appointments in our Brandon, Clearwater and Tampa hospitals and are available for phone consultations on cases that you feel may need radiation treatment.
We would like to thank our colleague from BluePearl in New York, John Farrelly DVM, MS, DACVIM-Oncology, DACVR-Radiation Oncology.
Cancedda S, Sabattini S, Bettini G, Leone VF, Laganga P, Rossi F, Terragni R, Gnudi G, Vignoli M. Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma. Vet Radiol Ultrasound. 2015 May-Jun;56(3):335-43.
Cancedda S, Marconato L, Meier V, Laganga P, Roos M, Leone VF, Rossi F, Bley CR. Hypofractionated radiotherapy for macroscopic canine soft tissue sarcoma: A retrospective study of 50 Cases treated with a 5 x 6 Gy protocol with or without metronomic chemotherapy. Vet Radiol Ultrasound. 2015 Nov 9 [Epub ahead of print]
Eckstein C1, Guscetti F, Roos M, Martín de las Mulas J, Kaser-Hotz B, Rohrer Bley C. A retrospective analysis of radiation therapy for the treatment of feline vaccine-associated sarcoma. Vet Comp Oncol. 2009 Mar;7(1):54-68.
Kung MB1, Poirier VJ, Dennis MM, Vail DM, Straw RC. Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma. Vet Comp Oncol. 2014 Nov 13. [Epub ahead of print]
Marcinowska A, Warland J, Brearley M, Dobson J. Comparison of two coarse fractionated radiation protocols for the management of canine pituitary macrotumor: An observational study of 24 dogs. Vet Radiol Ultrasound. 2015 Sep-Oct;56(5):554-62.
WANTED: Anemic Cats with Lymphoma
BluePearl Veterinary Partners in Tampa is currently recruiting patients for a trial to evaluate the safety and efficacy of a medication to manage anemia associated with high- or intermediate-grade lymphoma in cats undergoing chemotherapy.
- Cats, > 6 months old, male or female, >0 kg
- Stage III or IVa high- or intermediate-grade lymphoma (measurable as defined by RECIST criteria)
- Non-regenerative anemia with PCV 16-24%
- Concurrent or previous treatment with chemotherapy is permitted
- Stable concurrent medical conditions
- Adequate organ function
- Not pregnant, lactating or intended for breeding
- Fractious cats
- FeLV+ or FIV+ or any other active immunosuppressive systemic infection
- Significant neurological clinical signs
- Blood transfusion due to anemia within 30 days of screening
The study medication, diagnostic lab work, chemotherapy, and examinations for a 9-week modified L-CHOP will be provided at no cost to owners. Owners will be expected to keep an owner diary and comply with study protocols.
For more information, or if you have a patient who may meet the above requirements, please contact Drs. Jen Coyle or Curtis Kane or technicians Emily Kinsler, CVT, Rob Guevara, CVT, or Heather Nau, CVT at 813.933.8944.