December 2018   |   Volume 16   |   Issue 12

Cancer Pain in a Geriatric Cat

in this issue

in this issue

Palliative Management of Cancer Pain in a Geriatric Cat

Which Drugs Are Used to Treat Cognitive Dysfunction Syndrome?

Top 5 Steps to Practice Evidence-Based Veterinary Medicine

Feline Malignant Nerve Sheath Neoplasm

Acute Urethral Obstruction in a Cat

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Palliative Management of Cancer Pain in a Geriatric Cat

Beatriz P. Monteiro, DVM, University of Montreal

Paulo V. Steagall, DVM, MS, PhD, DACVAA, Université de Montréal, Quebec, Canada

Oncology

|Peer Reviewed

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Palliative Management of Cancer Pain in a Geriatric Cat

FIGURE 1 The patient on presentation

Luna, a 15-year-old, 8.6-lb (3.7-kg), spayed domestic shorthair cat with stable International Renal Interest Society stage 2 chronic kidney disease (CKD), was presented for evaluation of an enlarged right rostral mandible, decreased appetite, halitosis, and dysphagia of approximately a month’s duration (Figure 1). The owners also reported recent changes in behavior: Luna had become irritable and could no longer jump onto windowsills.

Physical Examination

On presentation, Luna was quiet and shy. Vital parameters were within normal limits (temperature, 100.8°F [38.2°C]; pulse, 160 bpm; respiratory rate, 36 breaths per min). She was subclinically dehydrated (5%), and her hair coat was greasy. The right submandibular lymph node was enlarged. BCS was 3/9, which was similar to previous visits, with apparently stable body weight. Systolic blood pressure was 140 mm Hg (reference range, <150 mm Hg). Because Luna refused to walk, mobility could not be assessed.

Oral pain was assessed through gentle palpation of the mandible. Luna showed signs of hyperalgesia (ie, increased pain sensation to a painful stimuli) and clear avoidance of palpation while hissing at the clinician. Because osteoarthritis (OA) was suspected, OA-related pain was assessed using the Client Specific Outcome Measures instrument (see Suggested Reading),1 which consisted of choosing and scoring 3 activities that were specific to Luna (ie, jumping onto the kitchen’s window sill in the morning, using the litter box after breakfast, jumping onto the bed in the evening). Luna performed these activities with severe, mild, and moderate difficulty, respectively. Although there is currently no validated instrument to assess quality of life that is freely available to veterinarians, a general quality-of-life assessment was performed by evaluating Luna’s ability to perform daily activities, appetite and grooming habits, and social interactions and temperament.2,3 Because Luna was showing progressively decreased levels of activity and socialization, it was determined that her quality of life was moderately affected.

CBC and serum chemistry profile results revealed mild anemia (hematocrit, 25%; reference range, 28%-47%) and elevated BUN (42.6 mg/dL; reference range, 11.5-30.2 mg/dL) and creatinine (2 mg/dL; reference range, 0.4-1.9 mg/dL) levels. Urine specific gravity was 1.029 (reference range, ≥1.035), symmetric dimethylarginine was 15 μg/dL (reference range, 0-14 μg/dL), and total thyroxine was 1.6 μg/dL (reference range, 1.0-4.4 μg/dL).

Poll

What are you most interested in learning regarding cannabinoids in veterinary medicine?


Diagnosis

Luna was anesthetized for additional diagnostics. Premedication was administered intramuscularly with a combination of acepromazine (0.02 mg/kg) and buprenorphine (0.02 mg/kg). Thoracic radiography and abdominal ultrasonography were performed with the patient under sedation and revealed no evidence of metastasis. Approximately an hour after premedication, general anesthesia was induced with propofol (5 mg/kg IV) and maintained with isoflurane (1.2%-1.3% expired concentration delivered in 100% oxygen using a nonrebreathing circuit). Intravenous fluids (3 mL/kg/hr) were also administered. A firm mass (1.2 × 2 cm) was identified on the right rostral mandible. Oral radiographs revealed marked osteolysis and periosteal proliferation. An inferior alveolar (mandibular) nerve block was performed using bupivacaine 0.5% (see Local Anesthetic Technique for Nerve Blocks). An incisional biopsy was performed at the junction of normal and abnormal tissues and submitted for histopathology. No attempts were made to surgically remove the mass, as the owners did not want to perform any invasive procedures and wished to only confirm diagnosis. Histopathology results were consistent with squamous cell carcinoma.

LOCAL ANESTHETIC TECHNIQUE FOR NERVE BLOCKS

For local anesthetic techniques of the oral cavity, generally, a maximum bupivacaine dose of 2 mg/kg is calculated, and the total volume is divided among all the local blocks to be performed; in Luna’s case, because only the inferior alveolar (mandibular) nerve block was performed, 0.3 mL of bupivacaine 0.5% was used. The inferior alveolar foramen can be located on the medial side of the mandible approximately halfway between the angular process of the mandible and the last molar tooth. Although the foramen can be difficult to palpate in cats, the block can often still be performed successfully using 2 imaginary lines to locate the mandibular foramen (ie, a line perpendicular to the lateral canthus of the eye can be crossed with another line that divides the dorsal and ventral teeth arcade). The ventral teeth arcade is parallel to the ventral portion of the mandible. The injection point should be located at the intersection of these 2 lines, and the needle should be inserted perpendicular to the ventral margin of the mandible using an extraoral approach (Figure 2). The inferior alveolar (mandibular) nerve block produces anesthesia of the mandible, including the teeth, lower lip, part of the tongue, and hard and soft tissues.10

Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.
Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.

FIGURE 2 Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.

Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.
Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.

FIGURE 2 Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.

FIGURE 2 Right lateral (A) and ventrodorsal (B) views of a feline skull to demonstrate the inferior alveolar (mandibular) nerve block technique. The technique should be performed using 27- to 30-gauge, 12- to 16-mm long needles, and a 1-mL syringe. The area of injection of the local anesthetic is indicated by the dotted blue circle. For the extraoral approach, the needle (represented by the red line) should be inserted perpendicular to the ventral margin of the mandible, with the bevel of the needle directed toward the medial aspect of the mandible. The local anesthetic should be injected close to the inferior alveolar foramen on the medial aspect of the mandible (solid blue circles). Prior to injection, aspiration should be performed to confirm that no intravascular injections are being performed. The local anesthetic should be injected slowly, and no resistance should be felt.

Poll

Do you use NSAIDs as part of long-term pain management in cats, including those with stable chronic kidney disease?


DIAGNOSIS:

SQUAMOUS CELL CARCINOMA

Treatment & Long-Term Management

Anesthesia & Acute Perioperative Analgesia

Opioids are safe at clinically acceptable dosages and are excellent analgesics.4 The combination of opioids and acepromazine reduces inhalant anesthetic requirements. Locoregional anesthesia with bupivacaine provides pain relief by blocking sodium channels and the consequent production and transmission of nociceptive stimuli (ie, pain transduction and transmission). Analgesia lasts approximately 6 hours with locoregional bupivacaine.

Luna was hospitalized for 36 hours and maintained on fluid therapy. Pain was assessed every hour for the first 8 hours and every 6 hours thereafter using the Glasgow Composite Measure Pain Scale, which includes evaluation of the cat’s behavior and facial expressions while undisturbed.5 A pain scale score equal to or higher than 5 (out of 20) is the recommended cut-off score for intervention (eg, with buprenorphine [0.02 mg/kg IV q6h]). During pain assessment 4 hours after recovery from anesthesia, Luna was tense and crouched, with facial expressions indicative of pain, based on ear position and muzzle shape; pain score was 7/20. Thus, buprenorphine (0.02 mg/kg IV q6h) was administered. In addition, Luna exhibited a normal appetite when offered soft food, suggesting that the previously reported decreased appetite had been due to oral pain, which was attenuated by analgesic management.

The owners opted for palliative analgesic treatment (see Treatment at a Glance), with the aim of improving quality of life. Treatment of cancer was declined after a thorough discussion.

TREATMENT AT A GLANCE

  • Chronic pain can be managed on an outpatient basis through both pharmacologic and nonpharmacologic means.
    • Pharmacologic therapy
      • For Luna, this included robenacoxib (1 mg/kg PO q24h) and gabapentin (10 mg/kg PO q12h). Tramadol (3 mg/kg PO q12h11) or amitriptyline (10 mg PO q24h) could also have been added to this patient’s analgesic protocol.
    • Nonpharmacologic management
      • Environmental enrichment tailored to the patient’s needs. In Luna’s case, this included the addition of scratch posts, toys, and condos; steps so she could have access to windows; play sessions (15-20 minutes of access to the backyard under supervision twice daily); brushing (10-minute sessions twice daily as tolerated); and administration of soft food.
      • Nonpharmacologic therapies might also include acupuncture and/or nutraceuticals (eg, fish oil or green-lipped mussel extract, glucosamine/chondroitin sulfate, polysulfated glycosaminoglycan [extra-label]).
  • Long-term chronic pain management should include treatment of breakthrough pain (eg, administering buprenorphine when oral medications and other treatments are not controlling the pain).2

Pain Management & Palliative Care

Luna’s potential sources of pain included cancer pain affecting the oral cavity and bone, as well as pain associated with OA, resulting in mixed inflammatory and neuropathic pain. Therapy was planned using a mechanism-based approach (ie, analgesics to counteract inflammatory and neuropathic pain mechanisms). Luna was discharged on long-term medication, including robenacoxib (1 mg/kg PO q24h [see Extra-Label Drug Use]) and gabapentin (10 mg/kg PO q12h). NSAIDs are excellent analgesics for inflammatory pain but are normally contraindicated in cats with CKD; however, recent research has suggested that NSAIDs may be safely administered long-term in cats with stable CKD.6,7 The decision to initiate NSAID therapy in cats with CKD, however, should be made on a case-by-case basis, and the risks and benefits should be carefully assessed.8 In Luna’s case, the benefits of NSAID therapy were determined to outweigh the risks, particularly because proper nutrition and hydration were being maintained. Gabapentin blocks Ca+2 channels and reduces neuronal excitability, and this drug has been shown to provide analgesia in cats with OA and is indicated in conditions that cause neuropathic pain.9

Nonpharmacologic therapy in the form of environmental enrichment was also initiated and included play sessions (15-20 minutes of access to the backyard under supervision twice daily), brushing (10-minute sessions twice daily according to Luna’s preference), and providing scratching posts, homemade toys and condos, and steps to give Luna access to windows. Other nonpharmacologic treatment modalities could include acupuncture and/or nutraceuticals (eg, fish oil or green-lipped mussel extract, glucosamine/chondroitin sulfate, polysulfated glycosaminoglycan [extra-label]). Long-term chronic pain management should include treatment of breakthrough pain (eg, administering buprenorphine when oral medications and other treatments are not controlling pain).2

Luna’s needs were approached from a welfare perspective to provide optimal pain management using pharmacologic and nonpharmacologic options.2,3

EXTRA-LABEL DRUG USE

Clinicians are advised to check local regulations of NSAID administration in their country of practice. For example, in Canada, robenacoxib can be administered once daily for the treatment of musculoskeletal disorders, and the duration of treatment can be decided on an individual basis12; however, in the United States, this drug is only labeled for administration for up to 3 days.13 If extra-label administration is performed, owners should be made aware and perhaps sign a written consent form.

Prognosis & Outcome

Luna’s prognosis was guarded to poor. Recheck visits were performed monthly. Despite pain management, disease was progressive and resulted in pathologic mandibular fractures. Luna’s quality of life could no longer be maintained as an outpatient, and she was euthanized 8 weeks after presentation (see Take-Home Messages).

TAKE-HOME MESSAGES

  • Oral and bone tumors cause severe pain, which can be controlled using a multimodal pharmacologic and nonpharmacologic approach.
  • Pain in cancer patients is multifactorial and can originate from the tumor itself, diagnostic procedures, therapies, metastatic disease, and/or concomitant painful conditions.
  • Owners should be involved in the treatment plan and management of chronic pain by administering analgesics and providing nonpharmacologic therapies.
  • Cancer pain may become refractory to treatment as disease progresses, and pain management may no longer be achievable on an outpatient basis, requiring hospitalization.
  • Euthanasia should be considered for cats with severe chronic pain and/or poor quality of life. Decisions should be made on a case-by-case basis.

CKD = chronic kidney disease, OA = osteoarthritis

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Top 5 Steps to Practice Evidence-Based Veterinary Medicine

Sebastian Arlt, Dr.med.vet, DECAR, Free University of Berlin, Berlin, Germany

Preventive Medicine

|Peer Reviewed

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Top 5 Steps to Practice Evidence-Based Veterinary Medicine

Veterinarians in all disciplines1 should use optimal diagnostics, interventions, and medications to examine and treat veterinary patients. However, many veterinarians may not be using the newest information to aid clinical decision-making.

The principles of evidence-based veterinary medicine (EBVM) provide structured methods for processing the large amount and different types of clinical trials, studies, and other information available and applying that information to clinical case management.2 In the context of a specific case, following the 5 steps of EBVM3 can help veterinarians avoid mistakes, be more circumspect in practice, and provide the best patient care.

1

Ask

Formulate a relevant and answerable clinical question.

It is important for veterinarians to recognize knowledge gaps and limitations when facing a specific case. Using treatment protocols simply because they have “always been used” is often not appropriate in the rapidly developing veterinary field. Accepting that more valid information is needed to make an appropriate clinical decision is the first step in using the concepts of EBVM.

After identifying a gap in knowledge, situations or concepts that are often complex should be broken down into a precise clinical question. For example, a veterinarian treating pyometra in a dog should not simply ask, How should I treat a pyometra case? Instead, the veterinarian should formulate a question that addresses all aspects of the case. The PICO approach is a practical way to formulate a question:

  • P: Patient, population, and problem
  • I: Intervention
  • C: Comparison or control
  • O: Outcome

In the pyometra example, the patient and problem element is a female dog with pyometra. Intervention would involve hysterectomy, whereas choosing to do nothing would serve as a control. A hysterectomy as intervention can also be compared with the choice to treat with progesterone blockers or antibiotics. Finally, the outcome is considered: Will the patient survive or maintain fertility? 

Considering each of the steps in the PICO approach leads to the precise clinical question, In a 6-year-old female dog with open pyometra and only moderate clinical signs and slight WBC elevation, does hysterectomy have a better survival rate as compared with treatment with progesterone antagonists and antibiotics? The clinician can then research surgical versus medical treatment for pyometra.

A PICO question can be adjusted to different situations, including treatment considerations (eg, What medication is best? Is there risk for negative reaction?) or diagnostic questions (eg, Which diagnostic test provides the most reliable results?).

2

Acquire

Access the best available information to answer your question.

With so much information available, it may not be practical to read all veterinary journals. Thus, veterinarians should develop skills to efficiently find relevant articles via literature databases (eg, PubMed, CAB Abstracts). After developing a PICO-based question, the terms determined in the PICO process can be used as search terms. In the pyometra case example, “pyometra in a dog,” “hysterectomy,” “surgical intervention,” “medical management,” “fertility,” and “antibiotics” could all be used to search for relevant data.

It can be difficult to determine whether an article or study will contain the expected information based on an abstract or title alone. Many journals charge considerable fees to access articles, making it difficult for veterinarians to decide whether an article is relevant and worth purchasing. To overcome these obstacles, some projects aim to provide knowledge synthesis, systematic reviews, and meta-analysis of journal content (see Suggested Reading).4 Meta-analyses summarize information and statistically analyze the results of different clinical trials relating to a specific topic to formulate concise and advanced conclusions. Systematic reviews aim to collect and interpret all available information on a specific topic without a statistical approach but with a defined and rigorous search method. Knowledge syntheses (also referred to as critically appraised topics) are standardized summaries of research evidence around a specific clinical question, usually generated from a specific case or problem. Inclusion of case reports in knowledge syntheses is uncommon, as they are prone to bias. No quantitative assignments exist for meta-analyses, systematic reviews, or knowledge syntheses.

A knowledge synthesis may be helpful if the specific clinical question is very similar to the posed PICO question. In other cases, reviews might provide a broader overview about different options and give helpful background information. Large-scale reviews of evidence, common in human medicine, would be helpful in veterinary medicine but are not generally available.

CHECKLIST 1

Checklist to Assess the Quality of Research on Diagnostic Tests

Evaluation of diagnostic tests should include examination of the usefulness of new diagnostic tests. Results of a new diagnostic test are typically compared with current gold standard outcomes to establish the sensitivity, specificity, and likelihood ratios for the new diagnostic test.

Study Design  
The disease/condition to be tested is clearly defined. 1 point
Clear thresholds for physiologic/nonphysiologic conditions are defined. 2 points
Clear inclusion/exclusion criteria for patients/samples are reported. 1 point
An appropriate number of patients/samples was included in the study. 1 point
The test procedures are described in detail. 1 point
The study was blinded. 2 points
Test Characteristics  
The test was compared to an acknowledged gold standard. 1 point
Sensitivity and specificity of the test are given. 2 points
Repeatability of the test is good (same results when test is repeated). 1 point
Possible bias or other problems of the test (preanalytical/analytical) are discussed. 1 point
Practical Relevance  
Quality of the test results is discussed in context to other diagnostic tools for the given disease/condition. 1 point
Applicability and reliability of the test in practice is discussed objectively. 1 point
Add the given rating points to obtain the overall rating score. ____ points
15-13 = very good, 12-10 = good, 9-7 = satisfactory, 6-4 = adequate, 3-2 = inadequate, 1 = fail

3

Appraise

Assess the quality of the relevant evidence found.

After reading a study, trial, or article, the clinician must assess the information’s quality. Evidence can be ranked from weak to strong based on methodology.5 The following questions may be helpful in assessing information5:

  • Is the information relevant to my clinical question or my patient(s)?
  • Is the study design appropriate to answer my clinical question?
  • Is the level of evidence and the quality of the paper good enough to rely on the results?

Checklists are available to guide veterinarians through determining whether the level of evidence and quality of the paper are good enough to rely on the results (Checklists 1, 2, and 3). However, checklists are not comprehensive and do not cover all possible scientific research approaches.6 The literature evaluation form (Checklist 3) can be helpful in assessing the quality of treatment information in a study but is not the only method available for determining quality. When using it to assess the quality of information, clinicians should first determine the evidence level (eg, meta-analysis, clinical trial, case report, expert’s opinion or experience). Quality criteria such as study design, information content, and objectivity should then be assessed.

CHECKLIST 2

Checklist to Assess the Quality of Reviews

Literature reviews in journals aim to objectively summarize recent knowledge on a specific topic. In general, these knowledge compilations can be helpful. However, sometimes it is unclear how cited publications were selected and what the authors based their conclusions on. This checklist aims to provide an objective assessment of bias in literature reviews.

Literature Search & Inclusion  
Literature search was conducted systematically via databases and is well documented. 4 points
The used search terms are documented. 2 points
More literature was searched in reference lists of acquired articles. 1 point
Inclusion and exclusion criteria for papers are well documented. 2 points
Assessment  
The quality of each paper was assessed systematically. 4 points
The findings and conclusions are discussed objectively. 2 points
Add the given rating points to obtain the overall rating score. ____ points
15-13 = very good, 12-10 = good, 9-7 = satisfactory, 6-4 = adequate, 3-2 = inadequate, 1 = fail

By assigning a subjective score for each area in the checklist and totaling these ratings to obtain an overall score (Checklists 1 and 2), an impression of the quality and practical applicability of the information in a given study or paper can be formed.

The methods section should be reviewed to determine the study type and whether possible bias was addressed appropriately. Common sources of bias in veterinary literature include a small number of animals, lack of or incomparable control groups, missing specifications of diagnostic procedures, or missing definitions of diseases. Earlier studies have shown that common flaws in many papers include poor reporting of essential information (eg, age and medical history of the animals in the study), small sample size, missing enrollment criteria, and missing information on allocation and blinding.1,7 These are all factors that determine the quality of information and should be considered when deciding whether a study or paper is reliable.3

It is not possible or necessary for the reader to recalculate all the statistics given in a paper. However, by assessing other factors, the clinician can make some determination of quality.

4

Apply

Implement the evidence into clinical practice.

After new information is proven to be of good quality, the information should be assessed to determine if it is appropriate for a patient’s condition. The availability of the suggested therapies, availability of equipment, the veterinary team’s skills, whether the circumstances of the study are similar to the patient’s circumstances, the owner’s wishes, and legal and ethical aspects should all be considered. In the pyometra case example, step 4 involves discussing intended treatment extensively with the owners, including potential complications and recurrence.

Any new clinical applications or approaches should be communicated to the veterinary team and the pet owner. Even small changes concerning specific cases, practice protocols, or other routines in the practice may have a large impact on clinical outcomes, the practice, and the clinician’s professionalism.

CHECKLIST 3

Checklist to Assess the Quality of Research on Interventions

Step 1: Evidence Level    
Meta-analysis (statistical combination of the results of several studies) 5 points
Clinical trial 3 points
Case report 2 points
Expert’s opinion or experience 1 point
Step 2: Additional Quality Criteria (Regarding the Corresponding Evidence Level)    
Meta-Analysis Agree  
The literature search was exhaustive and reproducible. 2 points
The included trials were comparable from a clinical point of view. 4 points
Trials of a high quality (eg, randomized, controlled, blinded) were included. 2 points
Results are discussed objectively and critically, including questions regarding comparability and publication bias. 2 points
Clinical Trial Agree  
The trial comprised a sufficient number of animals or samples. 2 points
Essential information regarding the animals are given (eg, number, breed, age, sex, inclusion criteria, housing). 1 point
The trial comprised an adequate control group. 3 points
The trial is randomized. 1 point
The trial is blinded. 1 point
Examinations and interventions are described in detail. Results are presented completely. 1 point
Adequate statistic procedures were used. Data is complete, or missing data is documented sufficiently. 1 point
Results are discussed critically. 1 point
The bibliography is adequate (extent and up to date). 1 point
Case Report Agree  
Essential information regarding the animals are given (eg, number, breed, age, sex, inclusion criteria, housing). 2 points
Examinations and interventions are described in detail. 2 points
Results are discussed critically. 2 points
The bibliography is adequate (extent and up to date). 1 point
Expert’s Opinion or Experience Agree  
Results are discussed critically. 1 point
The bibliography is adequate (extent and up to date). 1 point
Step 3: Summate Rating Points to Obtain the Overall Rating Score.   ___ points
15-13 = very good, 12-10 = good, 9-7 = satisfactory, 6-4 = adequate, 3-2 = inadequate, 1 = fail
From Arlt SP, Heuwieser W. Training students to appraise the quality of scientific literature. J Vet Med Educ. 2011;38(2):137. doi: 10.3138/jvme.38.2.135. Reprinted with permission from University of Toronto Press (https://utpjournals.press). © 2018 AAVMC. All rights reserved.

5

Assess

Evaluate the impact of the changes.

Because improving clinical practice is a never-ending task,8 clinicians should assess whether changes implemented as a result of EBVM really led to better outcomes. Although it is easy to reflect on cases in which something went wrong or that had an unexpected outcome, it is also important to reflect on what went well in cases with positive outcomes. Assessment can be as simple as a personal reflection on individual cases at the end of a busy day. A more thorough assessment could include a reflection on the PICO-based clinical question, answers found through research, and a comparison to the actual outcome of the case. Finally, a formal practice-wide audit based on these 5 steps could be conducted.

EBVM = evidence-based veterinary medicine

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Which Drugs Are Used to Treat Cognitive Dysfunction Syndrome?

Which Drugs Are Used to Treat Cognitive Dysfunction Syndrome?

Margaret E. Gruen, DVM, MVPH, PhD, DACVB, North Carolina State University

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Which Drugs Are Used to Treat Cognitive Dysfunction Syndrome?

Cognitive dysfunction syndrome is a chronic, progressive disease with a range of clinical signs, including disorientation, changes in social interactions, alterations in sleep–wake cycles, house soiling (in a previously housetrained pet), and changes in activity and learning.1 Cognitive dysfunction syndrome is characterized by neuronal loss and neuroaxonal degeneration.2 The neuroanatomic pathology in dogs and cats shares some characteristics with human Alzheimer’s disease,3,4 specifically β-amyloid accumulation, tau phosphorylation, and neuronal loss in the frontal cortex, cerebellum, and hippocampus.2,5-7 The most common signs of cognitive dysfunction syndrome in dogs include house soiling and an increase or decrease in social interactions8; the most common signs in cats include vocalization and house soiling.9 Both dogs and cats may show signs of anxiety or fear (eg, agitation), which may be a result of disorientation. These clinical signs, particularly being awake at night, can be detrimental to the human–animal bond. Older dogs and cats should be screened for cognitive dysfunction syndrome at annual visits and pet owners educated about the common signs.

Environmental enrichment, mental stimulation, and diet promote cognitive health as pets age. Therapeutics used to treat cognitive dysfunction syndrome are typically chosen to address clinical signs once they have been detected. There are no approved drugs for prevention of cognitive dysfunction syndrome, and only one drug has been approved for dogs.10 Use of drugs to provide supportive and complementary care can mitigate signs associated with cognitive dysfunction syndrome. Clinician understanding of the rationale and utility of available drugs is crucial, as is balancing medications, owner expectations, and potential drug interactions.

Drug decisions should be based on clinical presentation, and patients should be monitored for treatment efficacy. It can be useful to prioritize the presenting signs to address those most pressing; for example, anxiety and changes to the sleep–wake cycle are often addressed first.

Selegiline

Selegiline is the only FDA-approved drug for treatment of cognitive dysfunction syndrome. It is only approved for use in dogs, although use in cats has been described.11 Selegiline is an monoamine oxidase inhibitor (MAOI) that specifically inhibits monoamine oxidase-B. Its effects in the CNS include increasing phenylethylamine and slowing metabolism of dopamine (and other monoamine neurotransmitters). Selegiline may also decrease free-radical production and enhance free-radical scavenging.12 In clinical trials, selegiline was shown to improve sleeping, housetraining, and activity in dogs.13 It has also been shown to improve spatial memory in older laboratory-housed dogs14 and have positive effects on learning and attention.15

Formulation → Oral

Dose (dogs) → 0.5-1.0 mg/kg q24h (administered in the morning)

Dose (cats; extra-label) → 0.25-1.00 mg/kg q24h (administered in the morning)

Key Points

  • Improvement or stabilization of clinical signs may take 6 to 8 weeks.
  • If there are no adverse effects, owners should be encouraged to continue administering the medication for 2 months then reassess the dog’s status. Adverse effects reported in clinical trials included vomiting, diarrhea, hyperactivity/restlessness, ataxia, and disorientation.16
  • Concurrent use of selegiline with other MAOIs (eg, amitraz) or serotonergic drugs (eg, selective serotonin reuptake inhibitors, tramadol, trazodone) is contraindicated due to increased risk for serotonin syndrome.

Benzodiazepines

In older humans, benzodiazepines may be associated with postoperative cognitive decline and an increased risk for Alzheimer’s disease.17 However, the disease risk in humans increases with both length of treatment and half-life of the medication,18 and relevance in animals is unknown. Benzodiazepines may be useful in treating anxiety and agitation associated with cognitive decline in humans and may be helpful in treating this condition in dogs. Although a variety of benzodiazepines are widely available, those with a shorter half-life and no active metabolites are preferred.

Lorazepam

Lorazepam is a generally well tolerated benzodiazepine with no active metabolites. Its elimination half-life in dogs is approximately an hour. Side effects can include lethargy or idiosyncratic increases in activity or vocalization. Lorazepam may be beneficial at night for patients that exhibit night waking.

Formulation → Oral

Dose (dogs) → 0.025-0.200 mg/kg up to q8h

Dose (cats) → 0.025-0.050 mg/kg q8-12h

Nutraceuticals

Various nutraceuticals have been used to treat cognitive dysfunction syndrome. The following discussion is limited to those that have been studied in dogs or cats.

α-Casozepine

α-casozepine is a decapeptide derived from α S1-casein in milk. Though the mechanism of action is not completely understood, α-casozepine appears to be structurally similar to γ-aminobutyric acid. It has been studied primarily for efficacy in anxiety paradigms in cats and dogs19,20; in dogs, however, it was evaluated for equivalence against selegiline.20 α-casozepine may be useful in alleviating signs of anxiety that accompany cognitive dysfunction syndrome.

Formulation → Oral

Dose (dogs, cats) → 15 mg/kg PO q24h

Key Point

  • α-casozepine has not been evaluated for use in treating cognitive dysfunction syndrome, but it may be useful for treating comorbid anxiety.

Antioxidants & Phospholipids

Oxidative stress appears to have a role in cognitive disorders by causing damage to proteins and lipids in the brain. Vitamins E and B and resveratrol have antioxidant properties and have been incorporated into supplement combinations and diets. Phospholipids (eg, phosphatidylserine) have also been included for their role in cell signaling. Products that contain a mixture of antioxidants and phospholipids (eg, phosphatidylserine) are available. One such product has been evaluated in an open-label trial with a small number (n = 8) of dogs with cognitive dysfunction syndrome.21 Although positive effects were shown on signs of cognitive dysfunction syndrome,21 results should be followed with a larger, controlled trial. This product was also shown to improve performance in a memory task in a placebo-controlled study of laboratory beagles.22 Other supplement combinations are available outside the United States, one of which includes antioxidants, phosphatidylserine, and omega-3 fatty acids and has been shown to improve scores for house soiling, owner recognition, and number of hours awake during the day.23

Dose (dogs) → See package insert.

S-Adenosyl-L-Methionine Tosylate

S-adenosyl-L-methionine tosylate may help maintain cell membranes and regulate cellular functions. It has been evaluated for use in treating depression, osteoarthritis, and liver disease.24 It has also been shown to selectively improve performance on tasks of executive function in laboratory-housed dogs and cats with cognitive dysfunction syndrome.25 In cats, treatment was most successful in earlier stages of cognitive decline as compared with later stages.25

Dose (dogs, cats) → Dose divided by weight class (≤22 lb; 22-44 lb; >44lb)

Apoaequorin

Apoaequorin* is a calcium-binding protein derived from jellyfish. It is believed to have calcium-buffering effects that protect against cell death. When assessed for effects on attention and memory in laboratory-housed dogs, apoaequorin showed favorable results against both placebo and selegiline for select cognitive tasks, particularly selective attention.26

Dose (dogs, cats) → See package insert.

Key Points

Apoaequorin has not been evaluated for beneficial effects in cats but is available in a sprinkles formulation.

*Of note, the commercial product has been placed on indefinite backorder.

Drugs Available Outside the United States

Propentofylline

Propentofylline is a xanthine derivative licensed in parts of Europe for the treatment of signs associated with cognitive dysfunction syndrome in dogs. It acts as a phosphodiesterase inhibitor, inhibits the reuptake of adenosine, and decreases the production of free radicals. In a comparison trial, propentofylline did not increase locomotor activity in older dogs.27

Formulation → Oral

Dose (dogs, cats) → 3-5 mg/kg PO q12h

Nicergoline

Nicergoline is an ergot alkaloid derivative that acts as an α1- adrenergic antagonist and enhancer of cholinergic function via acetylcholine release. It is believed to have some neuroprotective and antioxidant activity. In a comparison trial, propentofylline did not increase locomotor activity in older dogs.27

Formulation → Oral

Dose (dogs, cats) → 0.25-0.50 mg/kg PO q24h (administered in the morning)

Diets

Two prescription diets have been labeled to support cognitive health in dogs, including:

Hill’s Canine b/d contains supplements of antioxidants, mitochondrial cofactors, and omega-3 fatty acids. Aged dogs fed this diet for 6 months showed improved performance (ie, fewer errors) on an oddity discrimination task as compared with aged dogs fed a control diet.28 Purina Pro Plan Veterinary Diets NeuroCare is supplemented with antioxidants, omega-3 fatty acids, and medium chain triglyceride vegetable oil. This diet was studied in a randomized controlled trial and was shown to improve signs of cognitive dysfunction syndrome in dogs following a 90-day feeding period, relative to baseline.29 In another study, dogs fed a diet supplemented with arginine, B vitamins, fish oil, and antioxidants performed better in tests of memory and discrimination.30 These specific diets are available for dogs, whereas supplementation has been incorporated into the diets of senior and geriatric cats. No veterinary diet has been specifically labeled to support cognitive function in cats. However, there is evidence that middle-aged cats fed a diet supplemented with antioxidants, arginine, B vitamins, and fish oil performed better in a series of cognitive tests as compared with cats fed a nonsupplemented control diet.31

MAOI = monoamine oxidase inhibitor

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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CB Insights Dec 2018

Calcineurin Inhibitors as Steroid-Sparing Agents

William Oldenhoff, DVM, DACVD, Madison Veterinary Specialists in Monona, Wisconsin

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Calcineurin Inhibitors as Steroid-Sparing Agents

In the Literature

Banovic F, Robson D, Linek M, Olivry T. Therapeutic effectiveness of calcineurin inhibitors in canine vesicular cutaneous lupus erythematosus. Vet Dermatol. 2017;28(5):493-e115.


FROM THE PAGE …

Vesicular cutaneous lupus erythematosus (VCLE) is a form of cutaneous lupus erythematosus that is seen mainly in collies and Shetland sheepdogs. VCLE has a distinctive clinical appearance, with lesions consisting of annular to serpiginous ulcerations primarily on the ventral abdomen, groin, and axillae, although mucocutaneous junctions and the concave aspect of the pinnae are commonly affected as well. As with many other autoimmune skin diseases, the treatment of choice has historically involved immunosuppressive doses of oral glucocorticoids. Although glucocorticoids are usually effective at inducing remission, side effects are common, and the long-term prognosis is guarded. As such, there is a need for safer long-term treatment options for VCLE. Calcineurin inhibitors (eg, cyclosporine, tacrolimus) are frequently used as steroid-sparing agents in dogs with autoimmune skin diseases, but there is a lack of published data examining the outcomes of these treatments.

In this study, the authors analyzed the outcomes of 11 dogs with VCLE that were treated with oral modified cyclosporine (5-10 mg/kg q24h). Initial therapies included systemic and topical antimicrobials (6 and 2 dogs, respectively) and oral corticosteroids (9 dogs); these treatments resulted in clinical improvement for several dogs, but none achieved clinical remission. After initiation of treatment with oral modified cyclosporine, complete remission was noted in 8 of the 11 dogs within 35 to 70 days. Complete remission was achieved in 2 additional dogs when the cyclosporine dosage was increased and topical tacrolimus was added. Relapse was often seen when cyclosporine doses were tapered. Three dogs were euthanized, but clinical remission was maintained in the remaining 8 dogs with oral cyclosporine and, occasionally, topical tacrolimus or pimecrolimus.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Cyclosporine appears to be a safer long-term treatment option for VCLE than glucocorticoids alone.

 

2

Once clinical remission has been achieved, clinicians should attempt to gradually taper medications to the lowest effective dose. Topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus) can be used to further reduce the need for oral cyclosporine. Although these topical products are initially expensive, one tube usually lasts several months, as only a small amount is used for each dose.

3

In dogs with immune-mediated skin disease, avoiding excess sun exposure is recommended. UV light has been known to exacerbate skin lesions in humans with CLE,1 and anecdotal information supports this effect in dogs.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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CB Mirataz Dec 2018

Ticks on Cats

Katie M. Clow, DVM, PhD, University of Guelph

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Ticks on Cats

In the Literature

Little SE, Barrett AW, Nagamori Y, et al. Ticks from cats in the United States: patterns of infestation and infection with pathogens. Vet Parasitol. 2018;257:15-20.


FROM THE PAGE …

The assumption that cats are careful groomers that can readily remove ticks has been studied in recent research. A handful of studies have suggested that ticks may pose a greater risk to cats in the United States than previously believed.1-3

In this study,* 796 ticks removed from 332 cats were submitted by 41 veterinary practices in 18 states, covering all 4 US geographic regions. Most ticks were identified as Ixodes scapularis (53.1%), Amblyomma americanum (28.4%), and Dermacentor variabilis (16.5%). Submissions occurred in all months, with peak submissions coinciding with peak activity of the tick species identified. Greater numbers of adult D variabilis and A americanum and nymphal I scapularis were submitted in May and June, whereas submissions of adult I scapularis peaked in October and November. The spatial distribution of submissions aligned with the known range of each tick species. I scapularis submissions were predominately from the northeast, A americanum submissions were mostly from the south, and D variabilis were from all regions. Tick-borne pathogens were detected in 17.1% of ticks; the most common pathogen was Borrelia burgdorferi found in I scapularis.

Patient age, sex, weight, spay/neuter status, site of tick attachment, and time spent outdoors were noted for each submission. Patients covered a wide age and weight range. Most were male and altered and spent >30% of time outdoors. Cats reported to be completely indoor also had ticks. Site of tick attachment varied by tick species, with I scapularis noted being predominately attached to the dorsal head and neck, D variabilis to the back and ears, and A americanum to the legs and feet, perianal area, and the abdominal, axillary, and inguinal regions.

Greater attention should be paid to tick burden in cats. Cats are susceptible to several tick-borne pathogens, including Cytauxzoon felis and Anaplasma phagocytophilum.4 Cats also live in close association with humans and other pets and may introduce ticks into shared environments.5 Year-round tick control should be considered for all cats, regardless of level of outdoor exposure.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Clinicians should be aware of the ticks prominent in their geographic region of practice; I scapularisA americanum, and D variabilis pose the greatest risk to cats in the United States. Risk is greater during peak tick activity (ie, May to June, October to November) and in geographic regions with known tick populations.

2

The possibility of ticks being present should not be ruled out in any feline patient, as ticks can be found on any cat, including those that do not frequent the outdoors. Location of tick bite varies greatly and is influenced by tick species.

3

Tick control should be considered for all cats, even those that have limited to no outdoor exposure.

 

*Funding to support this research was provided by a grant from Merck Animal Health, Madison, New Jersey, US, to Oklahoma State University.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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CB Dechra Dec 2018

Research Note: B-Tubes for Esophageal Strictures

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The current standard of care for esophageal strictures is repeated mechanical dilatation, which requires multiple anesthetic events. An alternative single-stage solution (ie, esophageal stenting) has been explored but has been associated with major complications. In this prospective study, an indwelling balloon dilatation esophagostomy tube (B-tube) was designed and investigated as a way to provide more frequent stricture dilatations while avoiding the persistent dilatation of stenting. B-tubes were placed in 9 dogs and 3 cats with benign esophageal strictures. The owners performed at-home inflations twice daily for approximately 6 weeks. The tubes were relatively well tolerated and maintained dilatation while in place. Modified dysphagia scores were significantly improved at final follow-up. These findings suggest that B-tubes offer an effective economical alternative, with decreased anesthetic time as compared with traditional balloon dilatation procedures.

Source

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


Research Note: Hepadnavirus in Immunocompromised Cats

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A novel hepadnavirus was discovered in lymphoma samples from an Australian domestic cat with concurrent high-grade, B-cell lymphoma and FIV. Genome sequencing and phylogenetic analysis identified the virus as belonging to the Hepadnaviridae family, the same family as that of the human hepatitis B virus. Presence of this virus was detected via PCR testing in whole blood samples from 6 of 60 (10%) FIV-infected cats and 2 of 63 (3.2%) cats not infected with FIV. Because this is the first report of a hepadnavirus infection in a carnivore or companion animal, further study is warranted.

Source

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Emerging Pathogens in Canine Infectious Respiratory Disease Complex

Jason W. Stull, VMD, MPVM, PhD, DACVPM, The Ohio State University College of Veterinary Medicine

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Emerging Pathogens in Canine Infectious Respiratory Disease Complex

In the Literature

Mitchell JA, Cardwell JM, Leach H, et al. European surveillance of emerging pathogens associated with canine infectious respiratory disease. Vet Microbiol. 2017;212:31-38.


FROM THE PAGE …

Canine infectious respiratory disease complex (CIRDC), a common cause of illness in dogs, is associated with a number of pathogens. Canine distemper virus, canine parainfluenza virus, canine adenovirus type 2, and Bordetella bronchiseptica have traditionally been associated with clinical disease related to CIRDC, but the importance of emerging pathogens is unknown.

This study* of European dogs investigated the prevalence of 4 emerging CIRDC pathogens (ie, canine respiratory coronavirus [CRCoV], canine pneumovirus [CnPnV], Mycoplasma cynos, influenza A [H3N8]) and their risk factors for exposure, infection, and clinical disease. Signalment data and samples from nasal swabs, oropharyngeal swabs, and serum were collected from 572 dogs from various sources (eg, shelters, households) and clinical groups (ie, clinically unaffected but exposed to acute CIRDC-affected dogs, acute and convalescent CIRDC-affected dogs).

Most study dogs (66.6%), including both pet and shelter dogs, had clinical CIRDC. Although CIRDC was noted in dogs vaccinated against CIRDC agents (ie, canine distemper virus, canine adenovirus type 2, canine parainfluenza virus), disease occurrence and severity were significantly reduced in these dogs. Overall estimated seroprevalence for CRCoV, CnPnV, and M cynos was high (47%, 41.7%, and 45%, respectively). Overall prevalence of CRCoV and CnPnV detected through PCR testing was 7.7% and 23.4%, respectively; presence of these pathogens was positively associated with clinical CIRDC disease and severity. M cynos and influenza A were infrequently detected by PCR (0.9% and 0%, respectively).

Pathogen seroprevalence and detection varied by source and country of origin. Shelter dogs were more likely to be seropositive for M cynos and CnPnV than were pet dogs, but prevalence was high for both shelter and pet dogs. Dogs that were seropositive for CnPnV were significantly more likely to be seropositive for CRCoV (and vice versa) and M cynos; this suggests frequent coinfection or cocirculation of these pathogens in dogs.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

CIRDC and associated infection from pathogens should be considered in dogs with consistent clinical signs.

 

2

Vaccination against CIRDC agents is important to reduce disease occurrence and severity, although owners should be warned that dogs may still develop (most commonly) mild disease.

 

3

The emerging pathogens CnPnV and CRCoV appear to play important roles in CIRDC in both shelter and pet dogs and should be considered when diagnosing and managing CIRDC. Pathogen testing is offered by some commercial laboratories. Clinicians should be aware of current trends in local CIRDC pathogen prevalence (eg, outbreaks, emergence), as these vary by region and should influence clinical suspicion and response.

*Sample collection and analysis for CRCoV, M cynos, and influenza A virus was funded by Zoetis Animal Health.

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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CB WSAVA Dec 2018

Blood Glucose Concentrations in Senior Cats

Andrew Bugbee, DVM, DACVIM, University of Georgia

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In the Literature

Reeve-Johnson MK, Rand JS, Vankan D, et al. Cutpoints for screening blood glucose concentrations in healthy senior cats. J Feline Med Surg. 2017;19(12):1181-1191.


FROM THE PAGE …

Similar to humans, many cats experience a period of carbohydrate intolerance before onset of fulminant diabetes mellitus (DM), termed prediabetes.1,2 Early recognition of this stage could enable clinicians to implement preventive measures (eg, weight loss), thereby preventing development of a diabetic state. An objective of this study* was to define a screening blood glucose (BG) concentration cutoff using healthy cats of ideal BCS (BCS, 4-5/9) that could be applied to a population of overweight and obese cats to help facilitate detection of a prediabetic state.

A population of cats of ideal BCS (n = 49) was used to establish a normal screening BG concentration range with an upper reference limit of 189 mg/dL. Screening BG was defined as the patient’s glucose concentration at the time of presentation and any time after eating. Samples were collected via marginal ear vein or pisiform pad stick, and BG concentration was measured using a glucometer calibrated for feline blood. When this screening BG concentration cutoff was applied to the obese cat group (BCS, 8-9/9; n = 26), no value was found to be above the reference limit, suggesting glucose intolerance was not present in this population.

The study also evaluated the impact of several factors on the screening BG concentrations obtained, including various patient characteristics (eg, age, BCS), stress exhibited during sampling, carbohydrate intake, and fasting BG concentrations (upper limit for cats with ideal BCS was found to be 116 mg/dL). None were statistically shown to alter screening BG concentration variability significantly.

In addition, the study investigated how different methods of blood collection or BG concentration analysis impacted variability of BG concentration readings. Glucometer readings differed when samples were immediately tested following an ear/pad prick as compared with jugular venipuncture. In addition, ear/pad prick glucometer readings differed from results obtained using jugular blood stored in preservative-containing collection tubes and from those of samples analyzed by an external laboratory.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

BG concentrations should be screened in senior cats presented for routine health assessment; a BG concentration >189 mg/dL is indicative of possible glucose intolerance.

 

2

Cats with a screening BG concentration >189 mg/dL should be reassessed within 4 hours to rule out stress hyperglycemia.

 

3

Persistent hyperglycemia in otherwise healthy cats may warrant determination of an 18- to 24-hour fasted BG concentration (upper reference limit, 116 mg/dL) and/or a glucose tolerance test to fully elucidate whether prediabetes is present.

4

Clinicians should adhere to a consistent BG concentration assessment methodology to minimize variability in results obtained.

  *This study was partially funded by Abbott Animal Health, Illinois, US.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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CB DVM Dechra Dec 2018
<em>Saccharomyces boulardii</em>: A New Probiotic Approach in Veterinary Medicine

Saccharomyces boulardii: A New Probiotic Approach in Veterinary Medicine

Anna Lena Ziese, MedVet, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig, Maximilian University of Munich

Jan S. Suchodolski, MedVet, DrVetMed, PhD, AGAF, DACVM (Immunology), Gastrointestinal Laboratory at Texas A&M University

Internal Medicine

|Sponsored

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<em>Saccharomyces boulardii</em>: A New Probiotic Approach in Veterinary Medicine
Brought to you by Nutramax Laboratories Veterinary Sciences, Inc.

The use of Saccharomyces boulardii has been established for multiple indications in human patients. With a better understanding of the impact of antibiotics on the intestinal microbiota, as well as increasing concerns surrounding antimicrobial resistance, a closer look at the yeast's potential impact on veterinary medicine is warranted.

Key Points

  • Indiscriminate use of antibiotics promotes development of antibiotic resistance, which poses a critical problem in public healthcare. 
  • Antibiotics cause alterations in intestinal microbiota, resulting in loss of microbiota function.1 Antimicrobial-associated dysbiosis may predispose patients for atopic, inflammatory, and autoimmune diseases.2,3 
  • Antibiotic-associated diarrhea (AAD) is a common presenting sign in veterinary and human medicine and occurs in up to 25% of human patients.4 In veterinary studies, 56% of healthy dogs receiving metronidazole5 and up to 85.7% of cats receiving amoxicillin-clavulanate6 developed worsening fecal scores. Administration of the probiotic yeast Saccharomyces boulardii helps in protection against and management of AAD in dogs.7 
  • In dogs with inflammatory bowel disease (IBD) managed with standard therapy (ie, diet, antibiotics, and steroids) and concurrent administration of S boulardii, clinical signs improved faster and more significantly than dogs managed with standard therapy alone.8

Antibiotics

Judicious Use

The indiscriminate overuse of antibiotics promotes antimicrobial resistance and transfer of resistance genes to pathogenic bacteria.1,9 In 2014, the World Health Organization published a global report10 with alarming data on the increase of antimicrobial resistance by specific pathogens. Resulting limited treatment options for bacterial infections and the subsequent potential for worse clinical outcomes and death pose a major problem in both human and veterinary medicine.

A study in healthy dogs evaluated the effect of a 7-day treatment with amoxicillin, an antibiotic commonly used in small animal veterinary practice. After 4 to 7 days of treatment, most dogs shed Escherichia coli resistant to several antibiotics.11 Therefore, due to the alarming emergence of antimicrobial resistance, a more judicious use of antibiotics is recommended.

Effects on Intestinal Microbiota

Antimicrobial agents also have pervasive effects on resident intestinal bacteria, which can result in dysbiosis,12 an alteration in microbiota diversity and composition.

Several studies have shown negative effects on the intestinal microbiome after antibiotic treatment in humans and animals. In one such study, cats receiving amoxicillin-clavulanate for 7 days were observed to have a decreased number of intestinal bacterial species, and the overall distribution of specific taxa had not recovered 7 days after antibiotic cessation.6 Another study revealed dogs treated with tylosin—an antibiotic commonly used for canine chronic enteropathy—for 14 days also had significantly decreased microbiota diversity and alterations in microbiota composition, particularly an increase in E coli-like sequences. Several bacterial taxa did not recover 14 days after antibiotic cessation, when the last fecal sample was collected in this study.13 Similar bacterial alterations with increased E coli have also been seen in dogs receiving metronidazole. Major disruptions in intestinal metabolism—including levels of bile acids and tryptophan—were observed and persisted until 4 weeks after cessation of metronidazole.5

Health Effects of Dysbiosis & Duration of Effects

The intestinal microbiome works as a metabolic organ and fulfills a variety of functions; a balanced microbiome is essential for host health. The microbiota modulates the host immune system, protects the host from invading pathogens, and provides nutrients to the host by metabolizing and fermenting various dietary components.14,15 Intestinal dysbiosis causes alterations in composition or diversity of bacteria as well as loss of microbiota function.1 Negative effects from loss of microbiota function include overproduction and translocation of bacterial toxins, pro-inflammatory stimulation of the immune system, reductions in beneficial bacterial metabolites (eg, short-chain fatty acids [SCFAs], secondary bile acids), and increased intestinal permeability.

Clinical signs vary between individuals and can range from mild GI signs to an increased risk for systemic diseases (eg, diabetes mellitus, obesity).2,16 Although clinical signs caused by antibiotic exposure usually resolve within days to weeks, alterations in diversity and composition can persist for longer periods. Studies in human medicine showed that alterations in intestinal microbiota and increased presence of bacterial resistance following antibiotic treatment can persist up to 4 years.17 Antimicrobial-associated dysbiosis is suspected to predispose patients for development of atopic, inflammatory, and autoimmune diseases, as well as IBD, asthma, or obesity in humans.2,3

MYCEQUIN™ chewable tablets for dogs from Nutramax Laboratories Veterinary Sciences, Inc. contain NMXAAD™ Proprietary blend of 10 billion CFUs (colony-forming units) of Saccharomyces boulardii plus beta-glucan. Beta-glucan is an immune-modulating compound that enhances innate defenses and stimulates both cell-mediated and humoral immunity. Beta-glucan has been shown beneficial in dogs with IBD.

General recommendation for MYCEQUIN use is 1 daily with antibiotics to help protect against antibiotic-associated gastrointestinal signs and 2 daily for chronic gastrointestinal conditions.

MYCEQUIN™ chewable tablets for dogs from Nutramax Laboratories Veterinary Sciences, Inc. contain NMXAAD™ Proprietary blend of 10 billion CFUs (colony-forming units) of Saccharomyces boulardii plus beta-glucan. Beta-glucan is an immune-modulating compound that enhances innate defenses and stimulates both cell-mediated and humoral immunity. Beta-glucan has been shown beneficial in dogs with IBD. General recommendation for MYCEQUIN use is 1 daily with antibiotics to help protect against antibiotic-associated gastrointestinal signs and 2 daily for chronic gastrointestinal conditions.

Saccharomyces boulardii as a Probiotic

Differences from Bacteria

S boulardii is a yeast strain first isolated in 1920 from the outer skin of tropical fruits in Indochina18 and, in recent decades, has garnered much interest as a probiotic agent. Probiotics are live microorganisms that, when consumed in adequate amounts, confer a health benefit to the host.19 S boulardii has favorable probiotic properties that differentiate it from bacterial probiotics.20 While bacteria are prokaryotes, yeasts are eukaryotic cells, which are up to 10 times larger than bacterial cells. Because of their differing cell wall structure, yeast cells are recognized by different host receptors than bacterial cell wall components, thus causing different antigenic responses. Yeast cells are resistant to low pH, bile salts, and GI enzymes, and S boulardii also has an optimal growth temperature similar to body temperature. These features allow for transit through the acidic stomach and are favorable to optimal colonization of the colon.21 An important property of yeast is its natural resistance to antibiotics, which allows it to be administered concurrently with antibiotics. In addition, administration of yeast does not promote development of antimicrobial resistant bacteria.

Mechanisms of Action of S boulardii

Several studies investigated the properties of S boulardii and found an extensive spectrum of mechanisms of action. S boulardii directly inhibits the growth of several pathogens (eg, Salmonella typhimurium, Yersinia enterocolitica) and has toxin-inhibiting properties through production of proteases able to degrade Clostridium difficile toxins and E coli endotoxin.18

In mice, treatment with S boulardii promoted faster restoration of the intestinal microbiota after disruption due to antibiotic treatment.22 Administration of S boulardii in humans was associated with increased intestinal SCFAs,23 which have anti-inflammatory properties, regulate intestinal motility, and are known to be an important source of energy.15 By increasing IgA levels and reducing pro-inflammatory responses, S boulardii is also able to modulate immune responses.18

In human medicine, major indications for the use of S boulardii are AAD and IBD (see Human Global Guidelines for Probiotics & Prebiotics). Clinical efficacy of S boulardii has also been observed in unclassified acute diarrhea, enteral-nutrition–related diarrhea, traveler’s diarrhea, irritable bowel syndrome, C difficile infection, and reduction of side effects of Helicobacter pylori therapy.18

Human Global Guidelines for Probiotics & Prebiotics

AAD and IBD are listed as evidence-based indications for adults and/or children in the Guidelines on Probiotics and Prebiotics published by the World Gastroenterology Organisation. Specific indications in children are acute gastroenteritis, prevention  of AAD, and reduction of side effects from treatment for Helicobacter pylori. Recommended dose of S boulardii in children for the prevention of AAD is 5-10 billion CFUs/day.26

Research in Veterinary Medicine

Antibiotic-Associated Diarrhea

AAD is defined as otherwise unexplained diarrhea that occurs in association with the administration of antibiotics. An estimated 25% of human patients treated with antibiotics develop diarrhea.4 While the exact incidence is currently unknown in veterinary medicine, antibiotic-associated GI side effects, including diarrhea, vomiting, and hyporexia, are believed to occur frequently and can result in owners discontinuing the course of antibiotics prematurely with implications for development of antimicrobial resistance.6,24

In numerous studies in human medicine, S boulardii significantly reduced the development of AAD.18 In a veterinary study of healthy dogs receiving lincomycin at 150 mg/kg IM (approximately 7 times the recommended dose in dogs), AAD was prevented in all dogs concurrently receiving S boulardii at 20 billion CFUs/day. In the control group that only received lincomycin without S boulardii, 75% of the dogs developed diarrhea with a mean duration of 6.5 days. In dogs that received S boulardii as soon as diarrhea occurred, a significantly shorter duration of diarrhea was observed with a mean duration of 2.9 days.7

Inflammatory Bowel Disease

IBD is characterized by a histologically confirmed inflammation of the GI tract with chronic recurrent GI signs.25 Animals with IBD require multimodal therapeutic approaches, and achieving relief of clinical signs can be challenging. Although the pathophysiology of IBD differs in humans and small animals, treatment with S boulardii in humans with IBD was associated with significantly reduced colonic permeability and relapse rate as well as significantly improved stool scores.18

One veterinary study investigated the effects of S boulardii in 20 dogs with chronic enteropathy confirmed as IBD.The dogs received S boulardii versus placebo concurrent to regular IBD therapy consisting of diet, antibiotics, and steroids ± other immunosuppressants. Clinical signs, evaluated with the canine chronic enteropathy clinical activity index (CCECAI), improved significantly in dogs administered  S boulardii compared with dogs given placebo. The body condition scores increased significantly only in the S boulardii group.8

Implications

These results indicate that S boulardii is a promising probiotic agent that can be used for protection against and management of AAD and in addition to standard therapy in dogs with IBD. Further studies are warranted to evaluate the efficacy of S boulardii against other GI diseases in small animals. 

Future Directions in Probiotic Research

Research on the intestinal microbiome has grown tremendously in recent years. The intestinal microbiome is a highly complex organ that affects the host’s metabolism and immune system; therefore, a balanced microbiome is crucial for host health. Therapies for the modulation of the intestinal microbiome are currently limited, mostly because of technical difficulties in evaluating the complex multiple immune and metabolic interactions between the microbiome and the host. It has become clear that individual probiotics have strain-specific effects on the host. For the best clinical outcome, probiotic products should be chosen based on scientifically proven effects for the particular clinical disorder.

AAD = antibiotic-associated diarrhea, BD = inflammatory bowel disease, SCFAs = short-chain fatty acids

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


Helping Owners Avoid Behavior Problems in Pets

Debra F. Horwitz, DVM, DACVB, Veterinary Behavior Consultation

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Helping Owners Avoid Behavior Problems in Pets

In the Literature

Todd Z. Barriers to the adoption of humane dog training methods. J Vet Behav. 2018;25:28-34.


FROM THE PAGE …

This article discusses the issues that may keep pet owners from adopting humane dog training methods. Humane dog training embraces the concept that only positive reinforcement and negative punishment techniques (ie, reward-based training) should be used. Other techniques such as positive punishment (ie, punishing an animal after a behavior has occurred in an attempt to discourage that particular behavior), use of aversive equipment (eg, choke or electric shock collars), and physical reprimands can be detrimental to efficient learning and have welfare implications on the dogs receiving them.1 The training method used has been significantly associated with the degree of attention-seeking behavior, fear-related behavior, and aggression; these behaviors have been shown to be highest in dogs trained with positive punishment.2

The information available to pet owners and owner unfamiliarity with terminology often leads them to inappropriate resources. Some owners are influenced by television celebrity trainers that highlight use of aversive methods. Lack of regulation in dog training adds to this problem; trainers may advertise their use of positive reinforcement and humane methods when, in reality, the techniques being used do not fit with the standard definitions of these methods. In addition, there can be disparity among training term definitions (eg, positive punishment).

Some professional organizations, including the UK Association of Pet Dog Trainers and the Pet Professional Guild, forbid their members from using certain aversive techniques. The International Association of Animal Behavior Consultants and Association of Pet Dog Trainers have adopted the least intrusive, minimally aversive approach. The American Veterinary Society for Animal Behavior has several position statements for the public, including use of punishment and dominance theory in behavior modification of animals.

Although veterinarians are in a position to counsel owners on these issues, not all veterinary colleges offer courses in veterinary behavior. Thus, veterinarians should educate themselves and research the credentials of trainers in their area.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Veterinarians can help owners understand the benefits and risks of certain training techniques and that positive reinforcement is the most efficient and humane way to train.

 

2

Owners should be informed of differences between trainers and the lack of reputable information on training and education of many individuals.

 

3

For cases in which behavior problems are affecting the human–animal bond or putting humans or other animals at risk, clinicians should consider referring to a board-certified veterinary behaviorist or certified applied animal behaviorist.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Positive Antinuclear Antibody & Coombs Test Results in Healthy Cats

Anne M. Barger, DVM, MS, DACVP, University of Illinois

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Positive Antinuclear Antibody & Coombs Test Results in Healthy Cats

In the Literature

Abrams-Ogg ACG, Lim S, Kocmarek H, et al. Prevalence of antinuclear and anti-erythrocyte antibodies in healthy cats. Vet Clin Pathol. 2018;47(1):51-55.


FROM THE PAGE …

Diagnosing immune-mediated diseases can be difficult in all species but can be particularly challenging in cats. Patients with systemic lupus erythematosus produce antibodies directed against molecular structures from the nucleus, cytoplasm, and cell membranes. These autoantibodies form immune complexes that can damage cells and interfere with cellular physiology. Clinical findings can include a broad range of signs (eg, fever, nonerosive arthritis, renal disease [primarily glomerular], skin lesions, CNS disorders). Fever and skin lesions are the most commonly identified clinical abnormalities in cats.

Antinuclear antibody (ANA) testing has shown that 16% to 20% of healthy dogs or dogs with other inflammatory diseases will have a positive test result.1 The prevalence of positive results in healthy cats, however, has not been clearly established. This study sought to determine the prevalence of positive ANA test and direct antiglobulin test (DAT) results in healthy cats. Sixty-one client-owned and 28 facility-owned cats were included. Of the 61 client-owned cats, 20% had strong ANA titers and 10% had weak ANA titers. Of the 28 facility-owned cats, only 4% had weak titers; no cats in this group had a strong titer.

Synovial fluid from a dog with systemic lupus erythematosus. The neutrophils contain many cytoplasmic inclusions. The cell is described as a ragocyte and can be identified in patients with systemic lupus erythematosus. Wright-Giemsa stain; 100× total magnification
Synovial fluid from a dog with systemic lupus erythematosus. The neutrophils contain many cytoplasmic inclusions. The cell is described as a ragocyte and can be identified in patients with systemic lupus erythematosus. Wright-Giemsa stain; 100× total magnification

FIGURE Synovial fluid from a dog with systemic lupus erythematosus. The neutrophils contain many cytoplasmic inclusions. The cell is described as a ragocyte and can be identified in patients with systemic lupus erythematosus. Wright-Giemsa stain; 100× total magnification

FIGURE Synovial fluid from a dog with systemic lupus erythematosus. The neutrophils contain many cytoplasmic inclusions. The cell is described as a ragocyte and can be identified in patients with systemic lupus erythematosus. Wright-Giemsa stain; 100× total magnification

The DAT, or Coombs test, is commonly used in the diagnosis of immune-mediated hemolytic anemia (IMHA). This species-specific test detects immunoglobulins and complement bound to patient RBCs. In cats, a negative DAT result has infrequently been identified in patients with IMHA, but a positive DAT result has been identified in cats with other inflammatory diseases such as pyothorax, pancreatitis, and FeLV.2,3 The present study showed that a low percentage of all the healthy cats were DAT-positive at a low dilution (1:2). These findings illustrate that healthy cats may have positive ANA or DAT results, but the prevalence of strong reactions is low.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Although ANA testing is a good diagnostic procedure, it is not a stand-alone test. It must be incorporated with the clinical presentation of the patient, as well as with other laboratory abnormalities (eg, suppurative arthritis, thrombocytopenia, hemolytic anemia, skin lesions).1

2

Similar to ANA testing, the DAT is not a stand-alone test and should be interpreted as part of a panel of tests, which should include CBC, and clinical suspicion of hemolytic anemia.

 

3

A positive DAT result may be seen in cats with inflammatory diseases other than IMHA (eg, pyothorax, pancreatitis, FeLV).

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Rabbit Neuter Techniques

Jonathan Miller, DVM, MS, DACVS (Small Animal), Oradell Animal Hospital, Paramus, New Jersey

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Rabbit Neuter Techniques

In the Literature

Duhamelle A, Tessier E, Larrat S. Comparative study of scrotal and prescrotal castration in pet rabbits (Oryctolagus cuniculus). J Exotic Pet Med. 2018;27(3):15-21.


FROM THE PAGE …

Rabbits, one of the more commonly owned exotic pets, are routinely presented for neutering. Three surgical techniques exist (ie, scrotal, prescrotal, abdominal), but no formal comparison of these techniques has been reported.

In this prospective, randomized clinical trial, 13 rabbits were neutered by either a scrotal or prescrotal technique. The inguinal rings were not closed in either technique. Surgery and anesthesia times, postoperative scrotal edema, licking, dehiscence, and infection were all assessed. Postoperative evaluations were performed at 8, 24, 32, and 168 hours postoperation.

A significant increase was found in the duration of anesthesia time in the scrotal group (median, 20.6 minutes) as compared with the prescrotal group (median, 17.9 minutes), and a significantly higher degree of edema at 8, 24, and 32 hours postoperation was identified in the scrotal group. The remaining variables were not significantly different. No infections or inguinal hernias were noted. Licking with incisional dehiscence was observed in 2 rabbits in the scrotal group. The prescrotal technique was associated with a shorter anesthesia time, likely due to an insignificant decrease in preparation and surgery times, and the prescrotal group also experienced less postoperative swelling. Both groups recovered well from the procedure.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Neutering should be considered in pet rabbits, as it has been known to be well tolerated in this species.

 

2

The prescrotal technique for neutering rabbits is superior to the scrotal technique for decreasing both anesthetic time and postoperative swelling.

 

3

Although the inguinal rings were not closed in either surgical group, no hernias were noted, suggesting this complication may be rare.

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Extended Use of Alfaxalone After Vial Puncture

Tamara Grubb, DVM, PhD, DACVAA, Washington State University

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Extended Use of Alfaxalone After Vial Puncture

In the Literature

Whitehead MC, Vanetten CL, Jacob ME, Harrison TM. Microbial integrity of preservative-free alfaxalone in a multiple-use system for two storage conditions and three handling techniques. Am J Vet Res. 2018;79(7):704-710.


FROM THE PAGE …

The United States Food and Drug Administration (FDA) mandates that preservative-free alfaxalone be discarded within 6 hours of vial puncture. Preservatives are commonly added to drugs to prevent bacterial contamination, which can occur when a needle punctures the vial stopper. Microbial contamination of drug vials has been identified in human cases of nosocomial morbidity and mortality.1 The FDA mandate is designed to preserve drug integrity and support patient safety, as the greatest risk for contamination occurs in multidose vials without preservatives, but failure to use the entire vial within the allotted time can result in drug wastage and increased costs.

Because alfaxalone is approved for use until 7 days after vial puncture in Australia,2 this study* evaluated the integrity of preservative-free alfaxalone in a multiuse system. Vials were refrigerated (at 39.2°F [4°C]) or stored at room temperature (71.6°F [22°C]). Samples were drawn by daily needle puncture through the rubber stopper of the vial or by 1 of 2 drug withdrawal systems that allowed a single puncture of the rubber stopper. Samples were incubated in soy broth ± subcultured on blood agar.

Although incidence of bacterial contamination was low, 6 of the 22 samples had bacterial growth. One isolate was identified on day 3 in a vial stored at room temperature from the repeated puncture group. The other 5 bacterial isolates were identified on day 7 or later in both refrigerated and room temperature samples. Four of the 6 isolates were from the repeated puncture group.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

It is possible to use preservative-free alfaxalone for up to 7 days, with the precaution of using specialized withdrawal equipment that allows only one puncture of the vial’s rubber stopper.

 

2

Use of an open vial for more than 7 days is not recommended, especially if the vial has multiple punctures. Although the study authors recommended drug refrigeration, the results do not support refrigeration as a means to decrease contamination.

3

Use of preservative-free alfaxalone more than 6 hours after vial puncture should be weighed against patient safety and standard of care. Appropriate patient care could be questioned if nosocomial infection is suspected following alfaxalone administration and the FDA’s 6-hour discard requirement has not been followed. Thus, the safest and most defensible option for clinicians is to use alfaxalone with a preservative, which was approved by the FDA in June 2018 and can be used up to 28 days after vial puncture.3

*This study was supported by Jurox Pty Ltd.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Feline Malignant Nerve Sheath Neoplasm

Joshua D. Warren, DVM, Red Bank Veterinary Hospital, Tinton Falls, New Jersey

Eric N. Glass, DVM, MS, DACVIM (Neurology), Red Bank Veterinary Hospital, Tinton Falls, New Jersey

Rachel Song, VMD, MS, DACVIM (Neurology), Red Bank Veterinary Hospital, Tinton Falls, New Jersey

Marc Kent, DVM, DACVIM (Internal Medicine, Neurology), University of Georgia

Oncology

|Peer Reviewed

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Feline Malignant Nerve Sheath Neoplasm

Socks, a 12-year-old, 14.8-lb (6.7-kg), indoor, neutered male domestic shorthair cat, was evaluated for a plantigrade stance in the left pelvic limb (Figure 1) of several days’ duration. Socks had no other known health issues, was current on vaccinations, and had no known trauma.

Physical Examination

There was a poor withdrawal reflex of the left pelvic limb characterized by an inability to flex the stifle/tarsus, with normal flexion of the coxofemoral joint. Withdrawal reflexes in the thoracic and right pelvic limbs were normal. Patellar reflexes were normal bilaterally. Mentation, cranial nerves, and postural reactions were normal, and hyperpathia was not observed on vertebral column palpation. Abnormal gait was limited to the plantigrade stance in the left pelvic limb.

The patient demonstrating a plantigrade stance in the left pelvic limb
The patient demonstrating a plantigrade stance in the left pelvic limb

FIGURE 1 The patient demonstrating a plantigrade stance in the left pelvic limb

FIGURE 1 The patient demonstrating a plantigrade stance in the left pelvic limb

Diagnosis

CBC, serum chemistry profile, and 3-view thoracic radiographs were normal. Serology results for FeLV, FIV, coronavirus, Toxoplasma gondii, and Cryptococcus neoformans were negative. MRI of the vertebral column from L5 through the caudal vertebrae and extending through the pelvic limbs revealed enlargement and abnormal homogeneous contrast enhancement of the left sciatic nerve between the biceps femoris and semimembranosus muscles from the level of the greater trochanter distally to the level of the mid-diaphysis of the femur. There was no mass effect. Initial fascicular biopsy and histopathology of the sciatic nerve revealed degenerative changes consisting of axonal loss, adipose infiltration, and fibrosis. There was no evidence of neoplasia or inflammation. After the initial biopsy, Socks was treated palliatively with analgesics and corticosteroids. No change in neurologic function was noted. Despite the initial biopsy results, neoplasia involving the sciatic nerve was considered likely. The owner was instructed to monitor for progression of weakness or development of other neurologic deficits.

Intraoperative photograph of the patient’s left sciatic nerve mass 28 months after initial presentation. Histopathology was consistent with MNSN. Proximal is toward the top and cranial to the left of the photograph.
Intraoperative photograph of the patient’s left sciatic nerve mass 28 months after initial presentation. Histopathology was consistent with MNSN. Proximal is toward the top and cranial to the left of the photograph.

FIGURE 2 Intraoperative photograph of the patient’s left sciatic nerve mass 28 months after initial presentation. Histopathology was consistent with MNSN. Proximal is toward the top and cranial to the left of the photograph.

FIGURE 2 Intraoperative photograph of the patient’s left sciatic nerve mass 28 months after initial presentation. Histopathology was consistent with MNSN. Proximal is toward the top and cranial to the left of the photograph.

Twenty-eight months after initial presentation, the neurologic examination was unchanged. However, a palpable mass was present in the left caudal thigh, and there was atrophy of the muscles distal to the stifle. CBC and serum chemistry profile remained unremarkable, but thoracic radiographs revealed a left cranial lung nodule. MRI of the pelvis and left pelvic limb revealed a 3.8 × 4.6 × 7.3 cm, multilobulated, ovoid mass located in the mid-thigh between the biceps femoris and semimembranosus muscles (Figure 2). As compared with the adjacent muscles, the mass was hyperintense on T2-weighted images, was hyperintense on T1-weighted images, and displayed strong, homogenous contrast enhancement. The owner declined definitive therapy (ie, pelvic limb amputation, hemipelvectomy, radiation therapy, chemotherapy) for the mass and elected palliative excisional biopsy of the mass. Histopathology following excisional biopsy was consistent with a malignant nerve sheath neoplasm (MNSN; Figure 3). No special stains were performed, as the pathologist was comfortable with the diagnosis of MNSN based on histopathology. Socks was treated postoperatively with analgesics (ie, tramadol [12.5 mg PO q12h], transdermal fentanyl patch [12 μg/hr]), antibiotics (ie, amoxicillin–clavulanic acid [62.5 mg PO q12h]), and corticosteroids (ie, prednisone [5 mg PO q12h]). The lung mass was not addressed further because the owner did not wish to pursue further diagnostics or treatment and the nodule was suspected to be a primary pulmonary neoplasm. Excision of the neoplasm provided analgesia, but neurologic status remained unchanged.

Histopathology of the mass was consistent with MNSN. A characteristic Antoni type A pattern consisting of bipolar spindle cells forming intersecting bundles, streams, and whorls can be seen. Not shown are the necrosis, atypia, and high mitotic rate that were noted in the patient and led to diagnosis of MNSN.
Histopathology of the mass was consistent with MNSN. A characteristic Antoni type A pattern consisting of bipolar spindle cells forming intersecting bundles, streams, and whorls can be seen. Not shown are the necrosis, atypia, and high mitotic rate that were noted in the patient and led to diagnosis of MNSN.

FIGURE 3 Histopathology of the mass was consistent with MNSN. A characteristic Antoni type A pattern consisting of bipolar spindle cells forming intersecting bundles, streams, and whorls can be seen. Not shown are the necrosis, atypia, and high mitotic rate that were noted in the patient and led to diagnosis of MNSN.

FIGURE 3 Histopathology of the mass was consistent with MNSN. A characteristic Antoni type A pattern consisting of bipolar spindle cells forming intersecting bundles, streams, and whorls can be seen. Not shown are the necrosis, atypia, and high mitotic rate that were noted in the patient and led to diagnosis of MNSN.

Forty-six months after initial presentation, examination revealed a firm, painful mass, measuring approximately 2 to 3 cm, dorsomedial to the left greater trochanter. The left plantigrade stance persisted. Socks had excessive flexion of the left coxofemoral joint during protraction and persistent poor withdrawal reflex. There was progressive atrophy and secondary contracture of the superficial and deep digital flexor and gastrocnemius muscles, resulting in hyperextension of the tarsus and flexion of digits. Left tarsal laxity and crepitus were palpable. Thoracic radiographs revealed enlargement of the left cranial lung nodule. Radiographs of the tarsus revealed osteopenia and proximal intertarsal joint subluxation. MRI of the left pelvic limb revealed regrowth of the mass (1.7 × 2.4 × 3.1 cm) at the level of the coxofemoral joint (Figure 4). Histopathology following excisional biopsy confirmed MNSN.

Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).
Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).

FIGURE 4 Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).

Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).
Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).

FIGURE 4 Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).

FIGURE 4 Repeat MRI 46 months after initial presentation revealed regrowth of the left sciatic nerve mass. Dorsal plane MRI T1-weighted images (inversion prepared following fast spoiled gradient echo) obtained after intravenous contrast medium administration. Figure 4A is dorsal to the pelvis. The contrast-enhancing enlarged sciatic nerve (solid arrow) that courses to a large mass (open arrow), in addition to the visible colon on the midline (asterisk), can be noted. Figure 4B is at the level of the coxofemoral joints (open arrowheads). A large, uniformly contrast-enhancing mass can be observed in the mid-thigh (open arrow). The colon is visible (asterisk).

DIAGNOSIS:

MALIGNANT NERVE SHEATH NEOPLASM

Treatment & Outcome

After diagnosis of MNSN, the owner again elected palliative excision of the recurrent painful neoplasm with adjunct corticosteroids (ie, prednisone [5 mg PO q12h]), analgesics (ie, tramadol [12.5 mg PO q12h], transdermal fentanyl patch [12 μg/hr]), and antibiotics (ie, amoxicillin–clavulanic acid [62.5 mg PO q12h]). Six months postoperatively, Socks appeared comfortable with static neurologic examination.

TREATMENT AT A GLANCE

Following initial biopsy

  • Palliative treatment with analgesics and corticosteroids
  • At-home monitoring for progression of weakness or development of neurologic deficits

28 months after initial presentation

  • Palliative excisional biopsy (elected by owner)
  • Postoperative analgesics, including tramadol (12.5 mgPO q12h) and transdermal fentanyl patch (12 µg/hr), antibiotics (ie, amoxicillin–clavulanic acid [62.5 mg PO q12h]), and corticosteroids (ie, prednisone [5 mg PO q12h])

46 months after initial presentation

  • Palliative excisional biopsy (elected by owner)
  • Adjunct corticosteroids (ie, prednisone [5 mg PO q12h]), analgesics (ie, tramadol [12.5 mg PO q12h], transdermal fentanyl patch [12 µg/hr]), and antibiotics (ie, amoxicillin–clavulanic acid [62.5 mg PO q12h])

Discussion

Plantigrade posture is associated with multiple neurologic and musculoskeletal causes,1 including:

  • Tibial nerve dysfunction with denervation of the tarsal extensor muscles (ie, gastrocnemius, superficial digital flexor). Endocrine-related neuropathies can affect the tibial nerve. In cats, diabetes mellitus can cause bilateral tibial nerve paresis/paralysis. In dogs, hypothyroidism may affect the tibial nerves. Resolution of tibial nerve paresis/paralysis may occur with treatment of the underlying endocrinopathy.
  • Partial or complete disruption of the common calcanean tendon. With disruption of the origin of the gastrocnemius muscle, the gastrocnemius muscle itself, or its tendon of insertion, the tarsus overflexes (ie, plantigrade stance) with weightbearing, and there is flexion of the digits. With tarsal flexion, the digits flex due to tension placed on the intact superficial digital flexor tendon as it courses along the caudal surface of the tarsus. In cases involving complete rupture of the calcanean tendon, plantigrade stance will be more complete and the digits normal.
  • Fracture of the calcaneus bone or tarsal luxation
  • Disruption of the long plantar ligament, originating at the plantar surface of the calcaneus, passing distally across the 4th tarsal bone, and attaching to the base of the 4th and 5th metatarsals

Differentials for a sciatic nerve tumor include primary neoplasms of nerves, which occur relatively infrequently in dogs and are rare in cats.2 Lymphoma is the most common secondary tumor involving nerves.2 Nerve tumors may arise from Schwann cells, perineurial cells, and intraneural fibroblasts and include schwannomas or nerve sheath tumors, neurofibromas, and MNSNs.2,3

Histologic features vary widely. Immunohistochemical stains may help in the diagnosis of schwannomas but were not used in this case.3 Diffuse, strong immunoreactivity against S-100 protein is seen in schwannomas, whereas neurofibromas demonstrate inconsistent immunoreactivity against S-100.3 MNSNs tend to have mitotic indices of at least 4, and necrosis is often present.3

Nerve sheath neoplasms typically progress slowly over weeks to months.2 MNSNs are often treated with surgical excision via limb amputation when the neoplasm involves a named nerve of the limb. Despite gross cytoreductive surgery, there is a high risk of recurrence.3 Although rare, pulmonary and regional lymph node metastases have been reported in a cat.4 Median survival times for cats with integumentary nerve sheath tumors with surgery alone has been noted at 645 days.5 The role of postoperative radiation therapy or chemotherapy has not been defined, but they are likely to provide beneficial effects.

MNSN = malignant nerve sheath neoplasm

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Acute Urethral Obstruction in a Cat

Acute Urethral Obstruction in a Cat

Marcella D. Ridgway, VMD, MS, DACVIM (SAIM), University of Illinois

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Acute Urethral Obstruction in a Cat

Availability of the drugs discussed here varies by region. Because many of them are available in the majority of the world, we are publishing this article for the benefit of readers in those areas.

Editor's Note: This article also appears in the December 2018 print issue of Clinician's Brief.

A 3-year-old neutered male domestic shorthair cat was presented after 2 days of pollakiuria and hematuria; 2 hours of vocalization, stranguria, and dribbling urine; and a single episode of vomiting.

Examination revealed 7% dehydration, tachycardia, and a firm, distended bladder; the remainder of the physical examination was within normal limits. CBC, serum chemistry profile, and urinalysis were unremarkable other than 4+ blood and presence of RBCs (TNTC) in the urine. Findings on abdominal ultrasonography likewise were unremarkable, with no evidence of calculi in the urinary tract.

The cat was treated with IV fluids, decompressive cystocentesis, and removal of an obstructive distal urethral mucus plug. An indwelling urinary catheter was maintained for 24 hours, then removed.

Which of the following drugs would be appropriate for this patient?

Based on the information provided, how would you grade the following drugs and why?

Do Not Use Proceed with Caution Safe

The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.

Buprenorphine

Correct ResponseSafeFeline lower urinary tract signs are painful and most commonly associated with feline idiopathic cystitis (FIC). They are considered best managed by opioids in the acute phases of disease. Of the opioids, buprenorphine has the benefit of multiple routes of administration, including sublingual and subcutaneous, and is suitable for at-home use. Alternative analgesics have some disadvantages; for example, the sedative butorphanol has limited analgesic activity, and fentanyl is linked to respiratory depression, bradycardia, and urinary retention and requires more intensive patient monitoring than does buprenorphine.

Meloxicam

Correct ResponseDo Not UseMultiple studies have failed to show a benefit of meloxicam treatment for the clinical course of FIC (eg, pain, duration) or for recurrence of urethral obstruction.1,2 Although renal injury is not apparent in this patient, NSAID use is contraindicated in patients with potential renal injury secondary to urinary outflow obstruction.

Prednisolone, dexamethasone

Correct ResponseDo Not UseAnti-inflammatory doses of prednisolone or dexamethasone have been shown to have no positive effect on the clinical course of idiopathic feline lower urinary tract disease (FLUTD) or FIC.

Amoxicillin–clavulanate

Correct ResponseDo Not UseEmpiric use of antibiotics is not warranted in cats with urinary obstruction. Bacterial UTI is uncommon in cats presented with FLUTD, FIC, or urethral obstruction, especially those between 1 and 10 years of age,3-5 and antibiotic administration does not prevent catheter-related UTI. Antibiotics should not be administered to these cats unless bacterial infection is documented by urine culture. If lower urinary tract signs recur postcatheterization, obtaining a urine sample for culture at a return visit 3 to 4 days later is recommended to determine whether bacterial infection was introduced as a consequence of catheterization.

Prazosin

Correct ResponseSafeα1-adrenergic blockers (ie, α1 antagonists), which can cause urethral muscle relaxation, are often used in cats with urethral obstruction because of the potential contribution of urethral spasm (ie, functional obstruction) to initial or recurrent urethral blockage. Prazosin is the antispasmodic of choice because of its rapid onset of action and demonstrated superiority to phenoxybenzamine in impacting patient outcomes2 and less sedative effect as compared with acepromazine. Although urethral relaxants may appear to benefit individual patients, controlled studies have not shown a positive impact for their use in cats with FLUTD or FIC, possibly because only the preprostatic and prostatic urethra are affected by smooth muscle relaxants. Hypotension is a potential adverse effect of all α1-adrenergic blockers used as urethral relaxants; these drugs should not be used in cats with hypovolemia or other conditions associated with pre-existing hypotension.

Phenoxybenzamine

Correct ResponseCautionAlthough phenoxybenzamine is commonly administered as a urethral relaxant in cats with urethral obstruction, this drug is less effective in reducing proximal urethral pressure than is prazosin or acepromazine and may require up to a week to show pharmacologic effect. In addition, cats with urethral obstruction treated with phenoxybenzamine were shown to have a significantly higher rate of recurrence of urethral obstruction as compared with cats treated with prazosin.2 As with prazosin, hypotension is a potential adverse effect, and thus phenoxybenzamine should not be used in cats with hypovolemia or other conditions associated with pre-existing hypotension.

Acepromazine

Correct ResponseCautionAcepromazine is effective in lowering proximal urethral pressures, but sedation is a common side effect. Because of its α1-adrenergic blocking effects, acepromazine can cause significant hypotension and thus should be avoided in hypovolemic patients.

Phenylpropanolamine

Correct ResponseDo Not UsePhenylpropanolamine is a sympathomimetic drug used to treat urethral sphincter mechanism incompetence secondary to urethral sphincter hypotonia in dogs and cats. However, use of an agent that increases urethral sphincter tone is contraindicated in patients with urethral obstruction. The urine dribbling in this cat is likely related to small amounts of urine escaping past the urethral obstruction rather than from urethral sphincter hypotonus.

Maropitant

Correct ResponseCautionAntiemetic therapy is not indicated in this patient, as vomiting was most likely the result of urinary bladder distension and pain triggering peripheral afferent pathways to the emetic center. This triggering condition can be resolved by bladder decompression and pain management. In addition, a single episode of vomiting often does not warrant pharmacologic intervention. In a minority of cats with obstructive FLUTD or FIC, antiemetic therapy may be needed if they suffer severe metabolic consequences (eg, acute renal injury, acid-base and electrolyte derangements) of urinary obstruction and subsequent ongoing emesis. In addition to its antiemetic effect, maropitant may provide a visceral analgesic effect6-8; however, its use as an analgesic in cats with lower urinary tract disease or urinary obstruction has not been evaluated.

Amitriptyline

Correct ResponseSafeStress is thought to contribute to the development of FIC.9-11 Amitriptyline, a tricyclic antidepressant that has both anxiolytic and analgesic action, may be beneficial in managing patients with severe or recurrent disease. Side effects include sedation, salivation, urine retention, thrombocytopenia, and neutropenia. Although there is insufficient evidence to support use of amitriptyline as a short-term medication, long-term use of this drug may be considered if or when other evidence-based methods of control—which include moist diet, veterinary therapeutic urinary diet, and multimodal environmental modification or environmental enrichment11—have not delivered a desired response.

FIC = feline idiopathic cystitis, FLUTD = feline lower urinary tract disease, TNTC = too numerous to count

References

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