2017 Merck Advanced Medicine Symposium - Audience Q&A from NAVC

2017 Merck Advanced Medicine Symposium - Audience Q&A from NAVC

The following are the speaker responses to questions from the audience during the Advanced Medicine Symposium, sponsored by Merck Animal Health, held Monday, February 6, 2017 at the NAVC Conference in Orlando, FL.

The opinions expressed in these answers are those of the speakers and do not necessarily reflect the official label recommendations and point of view of the company or companies that manufacture and/or market any of the pharmaceutical agents, products, or services mentioned.

Permethrin and Other Feline Toxicities

Garret Pachtinger, VMD, DACVECC

Does adding hydromorphone to dexmedetomidine improve emesis induction in cats?

Dr. Pachtinger:  While hydromorphone may result in vomiting (with or without dexmedetomidine) in the feline patient, my personal concern would be that the combined use of hydromorphone and dexmedetomidine would increase the risk for sedation and complications of emesis, such as aspiration pneumonia.

Is dexmedetomidine contraindicated after a certain number of hours following toxin ingestion in cats?

Dr. Pachtinger:  The goal of emesis as part of a decontamination protocol is to inhibit or minimize further toxicant absorption. The time frame of effective emesis will depend on the toxicant itself. Emesis induction should only be performed with 1) recent ingestion of a toxicant or 2) unknown time of ingestion in an asymptomatic patient. The more rapidly emesis is induced post ingestion, the greater yield of recovery of gastric contents. If several hours have elapsed since ingestion, the contents have likely moved out of the stomach and emesis will no longer be of benefit. That said, it does depend on the toxicant ingested. If the patient is asymptomatic, emesis can be performed up to 4 to 6 hours post ingestion. Again, this does depend on the toxicant ingested. If a gel cap medication is ingested, emesis is unlikely to be effective after 30 to 60 minutes, and while not potentially contraindicated, effectiveness may be quite limited.

What is the dose for dexmedetomidine when using it to promote emesis in cats?

Dr. Pachtinger:  Based on a study by Thawley and Drobatz (Assessment of dexmedetomidine and other agents for emesis induction in cats: 43 cases (2009-2014). J Am Vet Med Assoc. 2015 Dec 15;247(12):1415-8), the median dose of dexmedetomidine that caused emesis was 7.0 µg/kg (3.2 µg/lb; range, 0.96 to 10.0 µg/kg [0.44 to 4.55 µg/lb]). I personally would consider 7.0 to 10 µg/kg

For cats with vomiting/gastritis from toxin exposure do you use an acid blocker or gastrointestinal protectant? If so, which one?

Dr. Pachtinger:  H2-receptor antagonists are one option to consider; for example, famotidine at 1 mg/kg IV or PO every 12 to 24 hours. Proton pump inhibitors are another option, and some believe these are superior to the H2-receptor antagonists. Pantoprazole (1 mg/kg IV QD) or omeprazole (1–2 mg/kg PO or IV) are two options in this category.

Do you recommend reversing dexmedetomidine in cats after use?

Dr. Pachtinger:  If the clinician is concerned that the patient is sedate following emesis induction (successful or not successful), yes – I would then reverse the medication.

Is chronic renal failure a result of lily ingestion?

Dr. Pachtinger:  I think the best way to answer this question is that it is possible chronic renal failure may develop, but it is not the result of all cases. With early and aggressive intervention, it is possible there will be no longer term concerns. With that said, there have also been cases where on histopathology (biopsy, necropsy) mineralization of the kidneys, gastric mucosa, aorta, and myocardium were found, indicating a more chronic disease process.

Can you use parameters like two to three times maintenance for fluid rate?

Dr. Pachtinger:  Fluid therapy is a very difficult treatment modality to give a single, specific rate or volume. The best way to answer this in short is to say that maintenance can be calculated several different ways with two common discussions including 60 mL/kg/day or 2–3 mL/kg/hour. In these cases, diuresis with higher than normal fluid rates (~4-5 mL/kg/hour) can be initially considered. This will be variable based on not only the maintenance fluid rate, but also dehydration and ongoing losses. This will also depend on comorbidities, such as cardiac disease, which may limit your aggressiveness with the potential for fluid overload. This is the reason careful re-evaluation and repeat patient assessment is so imperative in our feline patients receiving fluid therapy, aggressive OR conservative!

What is the appropriate time frame to administer activated charcoal?

Dr. Pachtinger:  When administering activated charcoal, the sooner the better is the best answer.  While the simple answer is ASAP, in veterinary medicine it is often at least an hour following ingestion based on the transit time to the hospital, evaluation, potential emesis, and other variables. Administration of activated charcoal with a cathartic may still be effective 4 to 6 hours following ingestion. Moreover, the agent ingested, the potential for toxicity, and the understanding of enterohepatic recirculation may warrant repeat dosing of activated charcoal.

Can you repeat dosing of dexmedetomidine if the first dose does not work?

Dr. Pachtinger:  I do not know if this has been studied and while I do not have a right versus wrong answer, I have not yet clinically repeated a dexmedetomidine dose due to the concern for sedation.

In reference to lily toxicity, do you have a preferred fluid type?

Dr. Pachtinger:  I do not have one specific fluid type except to say my first-line therapy is an isotonic crystalloid (eg, Lactated Ringer's, Plasma-Lyte 148, 0.9% NaCl).

Are there any toxicity issues with sorbitol? It is in so many over the counter products!

Dr. Pachtinger:  While not toxic, remember that sorbitol is an osmotic cathartic that is used in products such as activated charcoal. For this reason, it can cause diarrhea and other gastrointestinal signs, but it is not “toxic.”

Would you use famotidine or another H2 inhibitor after inducing emesis? Do you have cats drink water to avoid esophageal damage from acid reflux?

Dr. Pachtinger:  I do not always use a H2-receptor antagonist or proton pump inhibitor for these cases. If I am concerned about esophagitis, gastritis, ulceration, and so forth, I would consider famotidine or omeprazole. I also do not have the patients immediately drink water to avoid esophageal damage, but if they are not “NPO” I certainly provide patients with water.

If dexmedetomidine doesn't work what do you do? Do you give up inducing vomiting?

Dr. Pachtinger:  This would depend on the agent/toxicant ingested. If there was a life-threatening ingestion of a toxicant, I would consider gastric lavage. Conversely, if a patient ingested an anticoagulant rodenticide, understanding that we have the antidote (Vitamin K), I may not be as aggressive using gastric lavage.

Do you use sucralfate suspension with household cleaner ingestion?

Dr. Pachtinger:  This would depend on the cleaner ingested and the clinical signs of illness.  If chemicals ingested resulting in oral cavity burns or ulceration, treatment of oral lesions would be symptomatic including pain management (opioids), sucralfate slurries, intravenous fluids to maintain hydration, and potentially provisions for nutritional support (eg, feeding tube).

Do you administer Vitamin E for Tylenol ingestion?

Dr. Pachtinger:  No, I do not use vitamin E for Tylenol (acetaminophen) ingestion.

Can acetylcysteine (Mucomyst) be given orally?

Dr. Pachtinger:  Yes.

Would you stay away from maropitant (Cerenia) if there is liver disease with Tylenol toxicity?

Dr. Pachtinger:  The caution with Cerenia and liver disease is that Cerenia undergoes hepatic metabolism as the primary mechanism for elimination. If hepatic function is impaired, the drug may accumulate in the body at higher than normal levels. If there is Tylenol toxicity without liver failure, I would consider Cerenia. If I am concerned that the liver is not functioning properly, I would use an alternate such as ondansetron.

Do you think N-acetylcysteine should be given IV for a loading dose then given PO for repeat doses? And is it better absorbed by one route versus the other?

Dr. Pachtinger:  I am not certain that we have the literature to support IV versus PO administration. Where I was trained, we used the IV method for hospitalized patients.

Can you give oral methocarbamol if you don't have injectable form?

Dr. Pachtinger:  Yes. But remember, onset of action may be variable and slower with oral administration versus the intravenous route.  Per the Plumb’s Veterinary Drug Handbook, “Limited pharmacokinetic data is available in veterinary species. In humans, methocarbamol has an onset of action of ≈30 minutes after oral administration. Peak levels occur approximately 2 hours after dosing. Serum half-life is ≈1–2 hours. The drug is metabolized and the inactive metabolites are excreted into the urine and the feces (small amounts).”

Where can I buy intravenous lipid emulsion for lipid therapy? Roughly how long is the shelf life?

Dr. Pachtinger:  I would contact your local veterinary supply company. While I recommend checking with the specific manufacturer you use, the Intralipid 20% made by Baxter and packaged in 500-mL bags has a maximum shelf life of 18 months. Once spiked, the bag is good for 24 hours.

Is SDMA test helpful in diagnosing NSAID toxicity?

Dr. Pachtinger:  I do not know that the SDMA test (IDEXX Laboratories) will help you determine if the potential renal disease is related to NSAID toxicity as compared with other causes. There are variables to consider as well. Dehydration will impact SDMA, BUN, and creatinine. If there is a high SDMA level, renal disease is considered to be definite.  

Does sucralfate cause nausea in dogs as much as it can in cats? Do you avoid its use in dogs, too?

Dr. Pachtinger:  Yes, I believe it does and for this reason I do not use it in every case with GI disease. I reserve sucralfate for patients in which the suspicion or evidence of esophageal or gastrointestinal ulceration is significant.

Lyme Disease Update

Steve Callister, PhD and Scott Stevenson, DVM, MSc

General Questions:

Given the theory or fact that Lyme disease can or may be sexually transmitted in humans, are there any indications that it could be casually transmitted in dogs (eg, mouth to mouth)?

Dr. Callister:  There is no evidence of sexual transmission of Lyme disease among either humans or dogs (studied extensively) and casual transmission in saliva is also not likely.

Is Lyme disease prominent in South Florida? Should veterinarians in Florida be vaccinating for Lyme disease? What month, if we see ticks starting in November?

Dr. Callister: South Florida has only small populations of Ixodes scapularis ticks and few harbor Lyme disease spirochetes – so risk is low.

Dr. Stevenson:  If you are seeing SNAP-positive dogs and Ixodes scapularis ticks on your patients, then vaccinating may be warranted. It is generally recommended to vaccinate near the start of your tick season, but Nobivac Lyme (Merck Animal Health) provides a high level of protection for at least one year so you could deviate from that timeframe.

How protective are oral flea and tick products against Lyme disease (ie, don’t the ticks have to bite and then will transmit Borrelia?)

Dr. Callister:  Numerous well-designed studies have confirmed high efficacy of one dose of Bravecto (fluralaner; Merck Animal Health) against fleas and ticks for at least 12 weeks.

Dr. Stevenson:  We have been very happy with the performance of the oral flea and tick preventives and believe they are equivalent, if not superior to, licensed topicals in prevention of tick-borne illnesses.

Are ALL species of ticks capable of transmitting Lyme?

Dr. Stevenson:  Only blacklegged (Ixodes scapularis) and western blacklegged (Ixodes pacificus) ticks are efficient Borrelia burgdorferi vectors in North America.

Diagnosis:

Do you advocate testing the attached engorged tick for presence of Lyme organisms?

Dr. Stevenson:  There is little useful information gained from sending engorged ticks for testing. A more useful strategy for confirming infection/exposure would be to test for anti-C6 antibodies (SNAP 3DX and 4DX tests, IDEXX Laboratories) after 6 to 8 weeks, especially if the dog was previously seronegative.

Are all the different Borrelia spp detected by Western blot or other common Lyme tests like the ELISA SNAP test?

Dr. Callister:  In the US, standardization of the Western blot for confirming Lyme disease has ONLY been validated for human infection. However, the SNAP test, which detects a highly specific antibody response that is only induced as the spirochetes disseminate in the mammal, has been well vetted for use during both human and canine infections. In addition, infection with all Borrelia spp that cause Lyme disease will induce a positive SNAP test result.

How soon after tick bite and infection will the SNAP test show positive?

Dr. Stevenson:  Antibodies are typically not produced until at least 4 to 6 weeks after infection, so early infection may be missed during this timeframe. However, most studies have shown almost 100% seroconversion after about 10 to 12 weeks. We test 6 to 8 weeks after the last known tick exposure.

What is the significance of persistence of IgM in humans with chronic Lyme?

Dr. Callister:  Most recent studies have demonstrated that persistence of IgM antibodies in patients with long-term disseminated (chronic) Lyme disease is rare. However, new IgM antibody responses may form against newly expressed proteins as the spirochetes disseminate (and express other proteins) during the course of illness.

Do you recommend a C6 test to confirm Lyme disease after a positive SNAP test?

Dr. Callister:  The quantitative C6 (Lyme Quant C6; IDEXX Laboratories) and SNAP tests each measure the same antibodies, but the Quant C6 titers can be used to monitor the response to treatment.

Can you see clinical signs of Lyme in dogs before a positive antibody on a SNAP 4Dx test?

Dr. Stevenson:  Typically, clinical signs are not apparent until about 2 to 5 months post infection and, in these instances, the SNAP is almost invariably positive.  

Dr. Callister: A small percentage (approx. 5–10%) of likely genetically susceptible dogs develop the whole spectrum of abnormalities within days to weeks after infection and some of these patients may still be seronegative.  

Why are C6 antibody titers not used in people?

Dr. Callister:  Actually, detection of anti-C6 antibodies is one of the best tests we have for confirming human infection and the test is commonly used, especially in highly endemic areas of the US. However, we do not typically use titers to predict active infection because researchers have shown that anti-C6 antibodies can persist for years, even after the spirochetes have been eliminated by antimicrobial therapy.

Treatment:

If you have a dog that has been exposed and has antibody but no clinical signs, do you treat?  \Why are we not afraid of a Lyme-positive asymptomatic dog becoming symptomatic? Why not treat to avoid potential future illness?

Dr. Stevenson: My overall goal is to prevent tick exposure and ensure clients are aware of the current literature. Specifically, we explain that most dogs that test positive for Borrelia burgdorferi may not develop clinical signs of Lyme disease, and the recommendation of the ACVIM Consensus Statement is to not treat asymptomatic dogs. However, researchers have also demonstrated that clinically asymptomatic dogs likely have spirochetes in the tendon sheaths that cause subclinical inflammation and there is no way to predict if the dog will subsequently become clinical. Therefore, if the owner still desires treatment, we comply with the condition that the owner must also comply with our prevention protocol to prevent future exposure.  

What do you do if Quant C6 remains elevated? Even after two rounds of 30-day treatment with doxycycline? When rechecking the Quant C6, what is considered successful treatment? We have some titers in the 600s that go down to the 300s 6 months later. Is that considered successful?

Dr. Stevenson:  This depends on the definition of “elevated.” IDEXX considers treatment “successful” (and we use this in our practice) if the post-treatment titer (6 months later) is <30 U/mL OR if the post-treatment titer is <50% of the original titer.  

Dr. Callister:  The strategy of monitoring titers over time can provide useful information concerning treatment efficacy, especially if the post-treatment anti-C6 antibody level decreases to an undetectable amount post treatment or the pre-treatment antibody titer was significantly elevated and the post-treatment antibody titer decreased significantly. However, it is also possible the pre- and post-treatment antibody levels will wax and wane unpredictably, even if the spirochetes are no longer present, especially if the pre-treatment antibody titer is relatively low.  

Do you run a Quant C6 test if the dog is symptomatic and you are going to treat anyway? What is your policy when a dog is positive on the SNAP 4Dx test but they have been positive in the past and been treated?

Dr. Stevenson:  I advocate Quant C6 testing if the dog is symptomatic because I want to 1) ensure the titer is high enough to support a Lyme disease diagnosis, 2) obtain a baseline to use to evaluate treatment efficacy (ie, undetectable or >50% reduction in titer within 6 months post treatment, and 3) to establish a baseline to help ensure the protocol to prevent re-exposure is effective. If the dog has previously been positive on the SNAP 4Dx, I recommend checking a Quant C6 to monitor the titer on an annual basis.

Please comment on the use of C6 titers to determine whether to treat asymptomatic 4Dx Lyme-positive dogs. How do you recommend we deal with these 4Dx-positive dogs? If the owner wants to treat but there is no protein in urine dipstick do you still do the Quant C6?

Dr. Stevenson:  I do not use a Quant C6 titer to determine treatment, especially if the dog is asymptomatic. There is no strong consensus, even on the ACVIM Lyme Consensus Statement, about treatment unless the infected dog has clinical abnormalities. I will, however, treat the dog one time if the client wishes, provided they then agree to focus on prevention of subsequent exposure/infection by educating themselves (importance of tick checks, ensuring clients are comfortable identifying ticks, knowing their seasonality, etc) and I also advocate using a labeled preventive (oral or topical) and annual vaccination. By using this strategy, my practice has decreased SNAP seropositivity from about 27% in patients not on our preventive program to <2% for those using our three-pronged approach, which has decreased confusion regarding “what to do with a blue dot” and also decreased the overall antimicrobial usage.

Vaccination:

What’s your opinion on vaccines using OspA only versus OspA and OspC?

Dr. Callister:  OspA-based vaccines were developed based on early research findings and, while they provide some level of protection, more recent studies demonstrated some significant shortcomings with the strategy.  Most importantly, the current OspA-based vaccines only provide protection against B. burgdorferi and, while this organism causes the vast majority of canine Lyme disease, there is the possibility that other more recently-described Borrelia genospecies may also cause Lyme disease in dogs. In addition, OspA is only expressed by the spirochetes in the midgut of “resting” ticks, so the OspA vaccine target disappears quickly once the tick begins feeding on the dog.  Therefore, OspA-based vaccines have a very short “window of effectiveness.”  

Vaccines that contain OspA and OspC offer enhanced protection. Most significantly, the addition of OspC (which also induces highly protective borreliacidal antibodies) greatly increases the “window of effectiveness” because the OspC target protein is expressed by the Lyme disease spirochetes as they migrate from the tick midgut to the salivary glands and also as they colonize the mammalian (dog) host. In addition, Novibac Lyme (Merck Animal Health) induces protective borreliacidal antibodies against a region (epitope) of OspC that is accessible even on viable spirochetes and is also conserved among the pathogenic Borrelia genospecies. Put simply, the addition of OspC provides more comprehensive protection than OspA alone.   

Did you vaccinate dogs that were positive? And if so, would you do it with active (clinical) infection?

Dr. Stevenson:  We will vaccinate clinically asymptomatic dogs as long as they are non-proteinuric. However, we do not vaccinate if the dog is clinically ill or proteinuric until after successful treatment or resolution of proteinuria.

Should we time our Lyme vaccines for certain times of the year if the effects are short-lived? Is it advisable to vaccinate dogs just prior to “tick season” rather than throughout the year (if other vaccines are due during the off season)?

Dr. Callister:  The efficacy of Lyme disease vaccines decreases over time after vaccination, so the early spring prior to emergence of questing ticks is ideal.  

Dr. Stevenson:  We typically vaccinate in the spring, especially our most high risk patients.  However, we also don’t hesitate to vaccinate year round as Nobivac Lyme vaccine is highly effective for at least 12 months.

What Lyme vaccine brand do you recommend that has a better coverage to protect dogs?

Dr. Callister:  I helped develop Nobivac Lyme and believe product works well.

Dr. Stevenson:  We have used Nobivac Lyme since 2010 and have been very satisfied with its efficacy as part of our three-pronged approach (tick checks, use of preventive, and vaccination).

We have seen painful injection site reactions with the Nobivac Lyme. Why and what do you recommend to prevent this?

Dr. Callister:  Unfortunately, slight swelling at the injection site that typically resolves within 48 hours may occur because of the need to stimulate a strong immune response to ensure comprehensive protection. If the recipient is a small dog, vaccination in the scruff is helpful.

Dr. Stevenson:  We typically prescribe an anti-inflammatory (eg, meloxicam) if there is a painful reaction. If the pet has reacted previously, we may administer an antihistamine prior to revaccination.

What is the duration of immunity for the Nobivac Lyme vaccine?

Dr. Callister:  Well-designed studies have confirmed that vaccination with Nobivac Lyme provides a high level of protection for at least one year.

How long overdue does the Nobivac Lyme vaccine have to be to require restarting with two boosters?

Dr. Callister:  After the dog has been vaccinated and boosted once, then annual revaccination should be sufficient to re-induce the appropriate protective immune response.  

Can you please discuss some of the risks of Lyme vaccines in terms of kidney damage or frequency of vaccine reactions?

Dr. Callister:  Whole cell Lyme disease bacterins have been commercially available since the early 1990s and, to date, I am unaware of any documentation of kidney damage caused by vaccination. However, swelling at the site of vaccination that typically resolves in less than 48 hours can occur in some recipients (<2%).

Dr. Stevenson:  We have not seen nephritis in vaccinated dogs.

Canine Flu: When Disaster Strikes

Natalie Marks, DVM, and Michael Mayer

(Note: Brenda Dines, DVM, also presented during this session.)

Did you have insurance and did you cover the cost of treatment for the sick animals?

Mr. Mayer: We don’t have insurance to cover lost income due to an outbreak. We didn’t directly reimburse any clients for their medical expenses but did offer credit for free nights of boarding or daycare. 

Were there any other boarding facilities with a flu outbreak in the local area around Hip Hounds at the same time?

Mr. Mayer: No other facilities that I am aware of.

How does one obtain media training?

Dr. Marks: There is a great resource online and through VIN: Media Training for Veterinarians, Western Veterinary Conference 2007, by James P. Humphries, BS, DVM, Colorado Springs, CO, USA. It gives the 50 interview tips that are very helpful to people new in the media arena. In addition, many state VMAs offer similar tracks or modules at their state conventions.

Dermatology Pictionary

Michael Canfield, DVM, DACVD

What products do you like to use to treat scabies in dogs and cats?

Dr. Canfield:  Selamectin (Revolution; Zoetis), ivermectin, and Advantage Multi (BayerDVM) have been the classics. As data is gathered, however, I suspect that the isoxazoline class, including fluralaner (Bravecto, Merck Animal Health), afoxolaner (NexGard, Merial), and sarolaner (Simparica, Zoetis), may end up being the go-to treatment for sarcoptic acariasis. Bravecto topical solution for cats may also end up being an option for our feline patients with scabies as well. Although it is extra-label use at this point, there have been a few publications on this topic. Parasites and Vectors is a free online journal where quite a few publications are available for your review. 

Treating Immune-Mediated Diseases

Andrew Mackin, BSc, BVMS, MVS, DVSc, DSAM, FACVSc, DACV

At what platelet count do you reach for vincristine in a dog with immune-mediated thrombocytopenia?

Dr. Mackin: Usually, the decision is based on a diagnosis more than a specific platelet count. I like to use it on the first day that I diagnose immune-mediated thrombocytopenia (IMT). Nearly always, on day one of IMT, affected dogs have very marked thrombocytopenia. I can’t recall the last time I diagnosed the initial onset of IMT in a dog with a platelet count of much above 20,000 to 30,000 platelets/µL. But, I guess if I diagnosed IMT with a count of over 50,000/µL, I wouldn’t give vincristine.

A dermatologist told me that you have to use brand name cyclosporine for at least a month to make sure it works before changing to a generic, because generics are less reliable. Would you agree?

Dr. Mackin:  I half agree. Most of the published veterinary dermatology studies using cyclosporine have used Atopica (Elanco) or its human equivalent, Neoral (Novartis).  So, if you want to replicate exactly what has been published, including replicating published success rates, use the brand name. If owners had unlimited money, I’d always do this. That way, if the animal didn’t respond, you can conclude “cyclosporine didn’t work” rather than “either cyclosporine didn’t work, or I’m using the wrong cyclosporine.” But I don’t feel strongly enough about it to blow the owner’s finances if they are on a more limited budget. Rather than saying “less reliable,” I’d say “less studied.”

Why are generics usually OK?

Dr. Mackin:

  • The modified (microemulsified) cyclosporines are not exactly the same as Atopica/Neoral, but they are similar.
  • One generic (Patriot) is actually Neoral under a generic name, but it is hard to find.
  • Another generic (Teva) seems to give as good as, if not better, blood levels as Neoral.
  • There is one dog atopy study that showed generic cyclosporine worked just fine.
  • If you are measuring blood levels or our T-cell assay, you have a “safety net” anyway, because you have some way of measuring if the drug gets into the system.
  • We don’t usually use therapeutic drug monitoring for skin, but, even with generics, we usually don’t need to, because the drug is concentrated in the skin (so any roughly comparable generic will usually work), and because you can just look at the skin (pruritus, lesions) to determine efficacy.
  • Generics are cheaper.

Does ketoconazole help to reduce the cyclosporine dose for immunosuppression (like the dermal application)?

Dr. Mackin:  Yes. Ketoconazole will reduce cyclosporine doses needed for all uses, including immunosuppression, so much so that you need to watch for cyclosporine toxicity.


 

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