2016 FALL: Xylitol Toxicity | Arterial Blood Gas | Current Heartworm Disease Topics | Toxicity Word Scramble | Meet Criticalist Megan Kaplan | Southpaw Fever and Other CE
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)|
We would like to thank our colleague from BluePearl in Washington, Linda Barton, DVM, DACVECC, for allowing us to use this article for Companion.
- 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.
Arterial Blood Gas – Why Don’t We Do Them More Often?
Myth 1: It’s too hard to obtain the sample.
Arterial blood gases may seem hard to acquire but actually are no harder in medium to large dogs than sampling a vein. Because the artery has a thicker muscular wall, it is can be slightly more difficult to pierce, but by using your finger to anchor the artery, you can make it easier. The most common place to try is the dorsal pedal artery on the medial aspect of the metatarsus. Another common location is the femoral artery or the lingual artery if under anesthesia. The femoral artery must be held off manually for 5 minutes after sampling. When you have a large dog under anesthesia, use this time to practice feeling an artery and even trying to obtain a sample in more controlled circumstances.
Myth 2: It’s too hard to handle the sample.
Arterial samples are handled the same way as venous with a few exceptions. Do not agitate an arterial sample as it can falsely elevate your oxygen content. You do not need to purchase a specific arterial sampling syringe, although those are nice. Aspirate heparin into a tuberculin then evacuate it; this will nicely receive the sample and prevent clot formation. The needle can be pierced into the rubber stopper of a lab tube to prevent further oxygenation. You have about 10 minutes to analyze the sample at room temperature, but if you need longer, the sample can be on ice for 30 minutes without degradation.
Myth 3: I need a special machine to analyze it.
I-STAT cartridges and some other in-house blood analyzers are designed to analyze oxygen and carbon dioxide concentrations. Check with the manufacturer if you are not sure, but any machine that measures pH and bicarbonate is likely to be able to analyze PaO2 and PaCO2.
Why bother if I have a pulse oximeter? Pulse oximeters are wonderful machines but have limitations. Sometimes they have difficulty picking up a signal in animals with pigmented mucosa, icterus or if the patient is not perfusing well. Measuring saturation of oxygen (SaO2) with a pulse oximeter only evaluates oxygenation and not ventilation. This can lead to false assumptions that animals with normal oxygenation do not have lung disease. Many patients can hyperventilate to tolerable SaO2 values but may collapse due to exhaustion if they have to keep hyperventilating.
|PaO2 mm Hg||SaO2%|
Myth 4: It’s too hard to interpret arterial blood gases.
With minimal practice, interpreting the basics of oxygenation and ventilation values is not difficult, i.e. determining that the patient is within normal limits or not. The two main values of importance are PaO2 (oxygenation) and PaCO2 (ventilation). The normal value for PaO2 on room air is 80-100 mmHg and for PaCO2, 35-45 mmHg. Most of us will want to perform an arterial blood gas to determine if a patient is hypoxic and needing supplemental oxygen. That would be verified by an arterial blood gas in the following two scenarios:
Scenario 1: The PaO2 is less than 80 mmHg. If you want to verify this finding with a pulse oximeter, you would see a SaO2 of less than 95%.
Scenario 2: The PaO2 is in the 80s but the PaCO2 is less than 30 mmHg. Finding this result indicates that the patient is hyperventilating significantly to normalize their oxygen level.
Both scenarios document a need for oxygen supplementation.
We would like to thank our colleague from BluePearl in Washington, Jennifer Waldrop, DVM, DACVECC, for allowing us to use this article for Companion.
More information about arterial blood gas interpretation can be found in many books and on Veterinary Information Network. You can also take labs locally and at national conferences to practice sampling and interpretation. We at BluePearl are also available to help in any way. Please let us know if you would like more information or if we can help if you have a difficult respiratory case.
As The Worm Turns: Current Heartworm Disease Topics, Part 2
Susan E. Yohn, DVM, DACVIM, DABVP
The American Heartworm Society (AHS) is considered the leading expert source on heartworm disease (HWD), providing expert guidelines detailing current information on effective procedures for the diagnosis, treatment and prevention of heartworm disease. This is the second in a two-part series discussing some topics of concern associated with the 2014 AHS guideline changes.
The dog tested HW antigen negative, but microfilariae were seen on a CBC differential review. What caused this discrepancy? There are several reasons why these discordant results could occur.
- Sub-threshold antigenemia: There needs to be one adult male and one adult female to produce microfilariae. All HW antigen tests screen for antigen produced by the female worm reproductive tissue. About one in five tests in patients with such low female worm burdens may be falsely negative. In endemic areas or areas of lower HW infection prevalence the false negative rate may be higher.
- Large worm burden: A dog with a large number of HW can also have a negative HW antigen test result. The infected dog’s immune system can produce an aggressive antibody response that binds all available HW antigen, leaving no antigen to react to the antibodies in the test kit. Usually in dogs with heavy worm burdens, other clinical and laboratory findings support the diagnosis of HWD. Clinical signs are usually present and pulmonary radiography shows radiographic evidence of HWD pathology.
- Other types of microfilariae: There are at least seven different filariae that can infect dogs. Dipetalonema reconditum is the most common filaria that can infect dogs around the world, including North America. Other filarial species are more regionally restricted but increasing international travel by dogs with their owners or importation of breeding stock increases the risk for other filarial species being imported. Careful morphologic examination of the microfilaria can help identify the species from a blood smear or filter test.
- Adult worms are dead: If an adult female dies naturally or due to adulticide therapy, microfilariae can continue to be found in circulation. Microfilariae can live several years. The number of microfilariae do decrease over time due to death, but remain a source for mosquito infection and transmission of HWD.
- Treatment by macrolides: HW antigen production can be suppressed in dogs that are infected with HW but are receiving macrocyclic lactone prophylaxis.
- Transplacental transmission or transfusion: Microfilariae can pass from the placenta to the fetus. It is also possible, but rare, that microfilariae can be passed from a HW-positive donor to a transfusion recipient. In both cases, the microfilariae are not of risk to the dog because the microfilariae can only develop into adults by passing through the molt stage in the mosquito.
What steps should be taken if the pet is HW antigen negative but microfilariae positive?
- The false negative HW antigen test should be confirmed by testing with an alternative test methodology. A different in-hospital HW antigen test or submission of a blood sample to a commercial laboratory for HW antigen testing should be done.
- The microfilariae should be examined morphologically to identify the species. Not all veterinarians or technicians have been trained for adequate microscopic differentiation. It is often best to submit the blood sample to a commercial laboratory to get microfilariae species confirmation. Some molecular methods have been developed that may help differentiate some of the more exotic filarial organisms.
- If there is no evidence of HW disease: The dog should be treated with a microfilaricide. Advantage Multi® Topical Solution for Dogs (imidacloprid + moxidectin) is the only FDA approved drug for the removal of circulating microfilariae in heartworm positive dogs. Ivermectin (50 mcg/kg) or milbemycin (500 mcg/kg) have also been used for successful clearing of the microfilariae. After appropriate therapy, the dog should be screened again for microfilariae. If negative, rescreening should be done in 2 to 4 weeks. If microfilariae recur, presence of adult worms should be assumed and adulticide therapy pursued.
- If there is evidence of HW disease: Discussion with the HW antigen test manufacturer should be pursued to consider advanced diagnostic testing of the blood sample to determine if the false negative test is related to antigen antibody complexing. If a dog with persistent D. immitis microfilariae and a negative HW antigen test has clinical signs, radiograph and echocardiograph findings, and other diagnostic tests (anemia, hyperglobulinemia, proteinuria, eosinophilia) supportive of a diagnosis of HWD, immiticide therapy should be pursued.
How significant is antigen-antibody complexing in contributing to false negative HW antigen testing?
Antigen-antibody complexing of HW antigen is not a new finding. There is more recent concern for this phenomenon because of concern for possible false negative test results in dogs with subclinical infections receiving the macrocyclic lactone HW preventatives. HW antigen-antibody complexing can occur in dogs with a high HW burden and has been reported in dogs on a slow kill HW protocol. Concurrent inflammatory diseases (atopy, concurrent tick-borne infections) can increase the risk of antigen-antibody complexing. The host antibodies can be HW specific or nonspecific antibodies, including those directed to intestinal nematodes. Heartworm antigen is bound by the host antibody preventing it from reacting to HW ELISA antigen tests. Studies have shown that pretreatment of serum (chemical or heat) breaks down these complexes and can increase the accuracy of the HW antigen test results. Routine treatment of blood samples for HW antigen testing is not recommended by the AHS. Pretreatment is not validated for the in-hospital test kits. Pretreatment can damage the HW antigen. If there are circumstances where HW antigen-antibody complexing is suspected, the veterinarian should contact the test kit manufacturer or the commercial lab where the HW test was submitted and discuss the availability of pretreatment.
A visit to the American Heartworm Society website can provide more detail about these and other topics related to HWD.
- American Heartworm Society. Prevention, diagnosis, and management of heartworm (Dirofilaria immitis) infection in dogs. 2014
- Drake J, Gruntmeir J, Merritt, H. False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventatives. Parasites & Vectors 8:68 2015.
- Rishniw M. Heartworm resistance and the slow kill protocol. MEDFAQ, Veterinary Information Network 2014.
- Rischniw M. Heartworm Dilemmas. MEDFAQ, Veterinary Information Network 2014.
Veterinary Toxicity Word Scramble
Toxicity cases are seen every day in veterinary medicine. How many of these can you unscramble?
FROM THE MEDICAL DIRECTOR
BluePearl Portal and More
Welcome fall! As sad as it is to watch summer go, the beauty of fall is inviting with all it has to offer, like hiking and bonfires. As always, our BluePearl hospitals are open 24/7 to help serve the needs of your clients and patients, even with those pesky seasonal issues, like using endoscopy to remove the core of a freshly picked apple.
Fall also brings the launch of the BluePearl Portal for all of our referring hospitals. The Portal provides password-protected, internet access to our medical records, to include, X-rays, CT images, bloodwork, medical notes and more, for past and present patients referred to our hospital by members of your clinical team. Records will be accessible 24/7 through our website and, based on your preferences, you may elect to also receive faxes and/or email messages. If you have any questions about the Portal, please reach out to Kristi Consolino, from our veterinary relations team, at email@example.com, 847.584.0200 (office) or 630.269.0298 (cell).
In other exciting news, Dr. Katherine Linger is returning to our BluePearl emergency team. Her name may sound familiar because she has been one of our fabulous relief clinicians, and she decided that being at BluePearl full time was the best option for her. We could not be happier.
Another addition to our team, Megan Bales, is joining Kristi Consolino in veterinary relations. Megan comes to us with an extensive veterinary background and is thrilled to join BluePearl. Kristi and Megan will be working together to ensure a smooth experience for your team when you refer patients to BluePearl.
Meet our specialist…
Megan Kaplan, DVM, DACVECC
Megan Kaplan, DVM, DACVECC
Prior to veterinary school, Dr. Megan Kaplan worked as an emergency veterinary technician, a job which ultimately convinced her that veterinary medicine and critical care were her future. Within her field, her particular interests include metabolic emergencies, Addison’s disease, feline urethral obstruction and gastrointestinal obstructions.
Dr. Kaplan’s education has taken her across the United States, with her undergraduate degree from University of Arizona and DVM from Colorado State University. She moved to New England for an internship in Massachusetts, then to the Midwest for a fellowship at the University of Minnesota. After a residency in Pennsylvania, she’s happy to be back out to the Midwest as a BluePearl criticalist in Chicago.
Our criticalist for the Skokie hospital, Dr. Kaplan is available for consultations and referrals on an alternate rotating weekly schedule, either Tuesday through Friday or Wednesday through Saturday.
Get to know Dr. Kaplan…
How long have you been with us?
I have been with BluePearl in the Chicago area for one year and have just recently relocated from the Northfield critical care team to Skokie.
Who is your favorite actor?
Denzel Washington because he can play any type of character.
What sports team do you root for?
Chicago cubs, of course!
If you were not in veterinary medicine, what would you be doing?
Traveling the world. I especially love the beach!
What is your favorite part of the day?
I really love being part of the learning experience for the interns, so rounding on cases and teaching the interns is easily my favorite part of the day. They are the future of veterinary medicine, and I feel honored be a part of their training.
SAVE THE DATE: January 29, 2017
Guaranteed Rate Field (US Cellular Field), Chicago
It will be cold outside, but the lecture halls will be warm at Guaranteed Rate Field, the soon-to-be-renamed US Cellular Field. Our daylong CE event, Southpaw Fever (previously known as Cabin Fever), will warm you up with beautiful views of the field, eye-opening CE topics and friendly faces. Save the date so you can join us for this exciting daylong CE event!
We also offer CE at our hospitals, other venues and even at your practice. Our CE to Your Door brings a CE topic of your choosing to your hospital team at a time and date that is convenient to your staff. For the most current information on our CE offerings, please visit our online calendar or contact veterinary relations team members Kristi Consolino at 630.269.0298 or firstname.lastname@example.org or Megan Bales at (847) 564-5775 or email@example.com.