Therapeutics

Antiplatelet Drugs

By Lisa Murphy DACVECC

Knowledge of the thromboembolic diseases has advanced significantly in veterinary medicine. Hypercoagulability is important to recognise since the development of thrombi can increase morbidity and duration and cost of hospitalisation, and in some cases lead to death. This will be a brief review of some of the common oral thromboprophylactic drugs used in veterinary medicine.

Types of thrombi

Before getting to the use of medications available to reduce the risk of thromboembolism in our patients, we’ll just spend some time on the two general types of thrombi and the causes of hypercoagulability in clinical practice. The current classification of thromboemboli is dependent on location.

Thrombi that form in the arterial circulation are composed primarily of platelets and fibrin while thrombi that form in the venous circulation are composed primarily of fibrin and entrapped erythrocytes. It is, therefore, reasoned that the platelet-rich thrombi in the arterial circulation are more likely to be initiated by platelet activation and thus, prevention of these thrombi is best provided by antiplatelet therapy such as aspirin and clopidogrel.

By the same reasoning, fibrin-rich thrombi in the venous circulation would be best prevented by anticoagulant drugs such as the heparins or rivaroxaban. For example in canine immune-mediated haemolytic anaemia (IMHA), most available evidence pertaining to thromboembolic complications is focused on pulmonary thromboembolism (PTE). The typical human model of PTE consists of pulmonary emboli broken from thrombi that have formed in the deep leg veins, or deep vein thrombosis. Dogs, of course, do not typically form thrombi in leg veins. The origin of the pulmonary embolus is often unclear and likely varies from patient to patient. The origin may, in fact, be the pulmonary circulation itself. As the thrombus initiating factors are difficult to predict in the dog, and canine IMHA patients have been found to have circulating activated platelets, prophylactic therapy that includes antiplatelet drugs is likely beneficial.

Risk factors for thromboemboli

What are the risk factors for our patients to develop emboli? Virchow’s triad describes the main factors which can predispose patients to thromboembolic events and includes endothelial dysfunction, hypercoagulability of blood and blood stasis/altered blood flow.  The following table includes some examples of factors in clinical practice that may predispose to thromboembolic events.

TE predisposition.png

Antiplatelet drugs

The main 2 drugs evaluated in veterinary medicine are aspirin and clopidogrel (Plavix®).

Aspirin

Aspirin is a cyclooxygenase (COX) inhibitor. Thromboxane-A2 is produced by platelets via the COX enzyme and is a potent platelet agonist.

A dose of 0.5 mg/kg/day in a dog can inhibit normal platelet aggregation in an in-vitro setting. However, 30% of dogs can exhibit aspirin resistance and thus will not experience any antiplatelet effect following aspirin administration. It is believed that platelets cannot manufacture additional copies of COX so the blockade induced by aspirin is likely for the life of that platelet (6 days +/- 1.1 in dogs and cats). This is how ultra-low dose aspirin protocols work, a small amount of aspirin given daily will result in a blockade of all platelet COX in the body. Studies in dogs have evaluated ultra-low dose aspirin (0.5 mg/kg PO q 24h) with TEG and showed that aspirin failed to mitigate hypercoagulability consistently.

Things can get more complicated when considering cats and there is little consistent evidence that aspirin is an effective antiplatelet agent in cats. This is likely because feline platelets undergo aggregation via several substances and the role of thromboxane is minimal. High dose aspirin in cats (15 mg/kg PO q 48hr) can decrease platelet aggregation but again these effects are not consistent and adverse effects may occur at this dose so it is not recommended. 

Clopidogrel

Clopidogrel is an antagonist of the P2Y12 receptor which is an ADP receptor found on the surface of the platelet. ADP is needed for platelet aggregation.

A dose of 1 mg/kg in dogs resulted in effective decrease in ADP-induced platelet aggregation as early as 3 hours post-oral administration. There are reports of human patients exhibiting resistance to the effects of clopidogrel but none such effects documented in veterinary patients. The biggest study in veterinary medicine evaluating aspirin vs. clopidogrel for thromboprophylaxis was for feline arterial thromboembolism (ATE). All the cats in the study had previously experienced an ATE 1-3 months prior and survived. Of the 72 cats evaluated, the median survival time of cats in the aspirin group was 190 days vs. over 400 days in the clopidogrel group.

Plavix NSAID.png

Rivaroxaban

Rivaroxaban is a newer anticoagulant drug. Unlike the other anticoagulants (warfarin, heparin), it comes in an oral form, requires less frequent dosage (typically q 12-24 h) and has a lower risk of haemorrhage. It is a factor Xa inhibitor which due to its specificity decreases the risk of bleeding.

A study evaluating its use in dogs with IMHA showed it to be well-tolerated but there is not enough evidence currently to know if it is superior to clopidogrel or aspirin for these dogs. Due to its specificity for factor Xa, normal coagulation panels (PT, PTT) cannot be used to monitor the drug’s effects and anti-fXa panels have to be performed. Few places aside from a few academic institutions have this capability. This medication is also more expensive than clopidogrel or aspirin which further limits its use at this time. 

Clotting.png

In conclusion, while there have been significant advances made in antiplatelet and anticoagulant therapy for dogs and cats further research is still needed. At this time clopidogrel is likely the most efficacious thromboprophylactic medication currently available for small animal patients. 
 

References:

Hogan, D.F., Fox, P.R., Jacob, K., Keene, B., Laste, N.J., Rosenthal, S., Sederquist, K. and Weng, H.Y., 2015. Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT). Journal of Veterinary Cardiology, 17, pp.S306-S317.

Kidd, L. and Mackman, N., 2013. Prothrombotic mechanisms and anticoagulant therapy in dogs with immune‐mediated hemolytic anemia. Journal of Veterinary Emergency and Critical Care, 23(1), pp.3-13.

Mellett, A.M., Nakamura, R.K. and Bianco, D., 2011. A Prospective Study of Clopidogrel Therapy in Dogs with Primary Immune‐Mediated Hemolytic Anemia. Journal of veterinary internal medicine, 25(1), pp.71-75.

Morassi, A., Bianco, D., Park, E., Nakamura, R.K. and White, G.A., 2016. Evaluation of the safety and tolerability of rivaroxaban in dogs with presumed primary immune‐mediated hemolytic anemia. Journal of Veterinary Emergency and Critical Care, 26(4), pp.488-494.

Rackear, D., Feldman, B., Farver, T. and Lelong, L., 1988. The effect of three different dosages of acetylsalicylic acid on canine platelet aggregation. Journal of the American Animal Hospital Association, 24(1), pp.23-26.

Weinkle, T.K., Center, S.A., Randolph, J.F., Warner, K.L., Barr, S.C. and Erb, H.N., 2005. Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993–2002). Journal of the American Veterinary Medical Association, 226(11), pp.1869-1880.

Yang, V.K., Cunningham, S.M., Rush, J.E. and Laforcade, A., 2016. The use of rivaroxaban for the treatment of thrombotic complications in four dogs. Journal of Veterinary Emergency and Critical Care, 26(5), pp.729-736.

Tomcat Urethral Obstruction Treatment Overview

By Lisa Murphy DACVECC

Causes of a urethral obstruction (UO) are varied but include idiopathic obstruction (which in more recent studies was > 50% of cases evaluated) and less commonly, uroliths and urethral plugs. Much research has also been done into the treatment of urethral obstruction in cats secondary to Feline Lower Urinary Tract Disease (FLUTD)/Feline Idiopathic Cystitis. Aside from actually removing the obstruction in the short term, few treatments have been proven to significantly reduce recurrence with upwards of 20% of cats experiencing a recurrence within 6 months. 

Here I summarise some of the common treatments. As always, please feel free to comment or to email me with questions (lisamurphyirish@gmail.com).

Intravascular volume resuscitation

Cats with urethral obstruction presenting in cardiovascular collapse require ‘shock doses’ of intravenous fluids (e.g. 10-20 ml/kg bolus followed by constant reassessment of the patient’s perfusion status repeating boluses as needed).

Studies looking at the use of different types of fluids, more specifically 0.9% sodium chloride (saline) vs. Normosol R (similar to buffered LRS or Hartmann’s solution), did not show any difference in outcome or clinically significant reduction in plasma potassium levels. Cats given NormR had a more rapid normalisation of their acid-base balance. For more on this topic see this podcast episode.


Hyperkalemia

Hyperkalemia occurs commonly in cases with severe obstruction from urine retention. Reduced glomerular filtration rate with secondary acute kidney injury (AKI) from the initial UO may also promote hyperkalaemia. These patients can present in shock-like states from severe hyperkalemia.

Typically, this is recognised by inappropriately severe bradycardia and cardiac dysrhythmia. Common dysrhythmias include atrial standstill and ventricular premature complexes. There is no set blood potassium level at which dysrhythmias will occur – although they are more common at levels > 8.5 mmol/l. Treatment is usually recommended above this level although some cats will not show clinically significant signs of hyperkalaemia even at this level. It is important to treat each patient as an individual.

Treatment options include:

  • Intravenous fluid therapy: improves renal perfusion and renal excretion of potassium; dilutes potassium in the extracellular compartment.
  • Calcium gluconate (0.5-1 ml/kg IV over 15 mins): can temporarily (approximately 20 minutes) reduce the cardiotoxic effects of hyperkalemia. It does not reduce plasma potassium levels and needs to be followed up with definitive management.
    • [S Jasani: the risk-benefit profile for the use of calcium gluconate in cats with clinically significant hyperkalaemia is very favourable in my opinion. I encourage a liberal approach to administer this therapy, potentially more than once.]
  • Dextrose (glucose) (0.5-1 ml/kg IV) and insulin (0.5 u/kg regular (neutral, soluble) insulin) to drive potassium into the intracellular compartment. Although both substances have a fast onset of action, use of insulin requires close monitoring of blood glucose over subsequent hours.

Decompressive cystocentesis

There has been much controversy about the safety of this procedure in these patients and until recently I definitely was in the camp of never doing this. Nowadays I will discuss the potential risks of this procedure with owners where I consider the procedure necessary.

Advantages of this procedure include:

  • Buying time for the patient by helping correction of the electrolyte derangements at least temporarily until a more definitive treatment can be performed
  • Potentially may help with unblocking
  • Rapid relief of symptoms
  • Need for minimal to no sedation
  • Helping to restore glomerular filtration which helps reduce worsening kidney injury

Potential risks of this procedure include:

  • Bladder rupture. However, in a retrospective study of 47 cats who had this procedure performed, no cat developed a ruptured bladder. An indwelling catheter was placed following decompressive cystocentesis in these cats and they were managed as standard thereafter.
  • Uroabdomen. A published study evaluated the use of repeat decompressive cystocentesis in cases where owners did not have the finances to pursue indwelling urinary catheter placement. Of the 15 cats evaluated, 73% were discharged, some of which had more than ten cystocentesis procedures performed. Of the non-survivors, three did develop uroabdomen and one haemoabdomen. Non-survivors also tended to have higher creatinine and required more frequent cystocentesis so perhaps this procedure should be avoided in sicker cats.
    • [S Jasani: information from this study has been shared here as it relates to the topic under discussion. However, I personally have very serious welfare concerns about this study protocol and remain to be convinced that an alternative more patient-friendly yet affordable protocol could not have been implemented.]

[S Jasani: as with Lisa, I do not promote the use of decompressive cystocentesis as first-line treatment. If performed, please be sure to drain the bladder as fully as possible to achieve maximum benefit possible.]

Catheter types and size, does it matter?

Is there a perfect catheter? The short answer is we don’t know. Each type of catheter has their own advantages and disadvantages.

  • Polyprolylene (or ‘Tom cat’) catheters are one of the more rigid options. They can help relieve the obstruction but also have higher risks of urethral trauma. They are likely uncomfortable for the cats if they are left indwelling.
  • Polyvinvyl (red rubber) catheters are commonly placed after the obstruction is relieved. They are much less irritant and offer more comfort for the cat.
  • More recent is the ‘Slippery Sam’ or polytetrafluroethylene which is very useful for unblocking without causing too much irritation to the urethra. However, it only comes in one size (3.5fr) and one length. Furthermore, the connection apparatus for this can be difficult and come apart easily. Please note that while we know some people still do this, some years back the manufacturers changed their recommendation to say that these catheters should not be left indwelling.

As far as catheter size, the jury is also still out. The 5fr catheter has the potential benefits of less luminal obstruction from clots, less likelihood of the cat urinating around it, and easier flushing of saline. However, one study looking at the use of 3.5fr and 5fr urethral catheters showed higher reobstruction rates with 5fr catheters within 24 hours (19% with 5fr vs. 6.7% with 3.5fr). This study was retrospective so the effects of different aetiologies of UO and differences in disease severity are difficult to interpret.

Finally, there is the question of how long to leave an indwelling catheter in place. In general, I would recommend leaving it in place at least until the cat’s blood work abnormalities have resolved and the urine grossly looks clear. No benefit has been proven on whether to leave it in for 24 or 48 hours.

Antibiotics

Depending on the study you read, bacteriuria has been shown in anywhere from < 2% up to 40% of cats with UO. What is known is that ‘prophylactic’ antibiotics do not prevent the development of urinary catheter-associated infections. In general, the younger a UO patient the less likely they have an infectious cause or component although they may develop one while the catheter is indwelling. Urine microbiology could be considered at the time of catheter removal or 3 days post removal. The practice of submitting the tip of the catheter for microbiology is also difficult to recommend because the tip has a high contamination rate which could cause false positives.

Urethral relaxants 

Medications most commonly used for this include acepromazine, phenoxybenzamine and prazosin which mainly function via alpha-1 antagonism leading to smooth muscle relaxation. Since smooth muscle is only present in the proximal third of the penile urethra these relaxants may not be very effective. One study showed a possible benefit of prazosin vs. phenoxybenzamine with lower recurrence of UO rates. A more recent study showed no beneficial effect of prazosin vs. placebo for the incidence of recurrent UO. 

Anti-inflammatories

Several anti-inflammatories have been studied for UO. Cats given prednisolone vs. a placebo did not show any improved survival. More recently, a study evaluating the use of meloxicom in cats with UO showed no difference in recurrence of UO or recovery from clinical signs compared to cats given a placebo. At this time, there’s no evidence showing a reduction in recurrence of UO with the use of anti-inflammatories. Intravesicular administration of pentosan sulphate, which is a glycosaminoglycan, also did not result in reduced recurrence or clinical signs.

Amitriptyline 

Amitriptyline is a tricyclic antidepressant which has anticholinergic, anti-histaminergic, sympatholytic, analgesic and anti-inflammatory properties. It has been used for human interstitial cystitis cases. Some studies have been performed evaluating this drug in non-obstructive FLUTD cases and have not shown any improvements. In one study, it may have increased the risk of FLUTD recurrence.

Post-obstructive diuresis

Post obstructive diuresis is an uncommon phenomenon that can occur in these patients. It may occur due to several factors including:

  • accumulation of osmotically active substances in the blood
  • tubular epithelial dysfunction
  • medullary washout
  • antidiuretic hormone dysfunction
  • increased natriuretic factors accumulating during obstruction 

Typically it is recognised by increased urine production (> 2ml/kg/hr). In one study, it tended to occur within 6 hours of resolution of the UO via a urinary catheter.  This study also showed cats with an admission pH of < 7.35, hyperglycaemia, hyperosmolality and azotaemia were more likely to experience this phenomenon. In some cases, the diuresis can last several days (one cat in the aforementioned study experienced it for 84hr).

Post-obstructive diuresis can lead to dialysis disequilibrium syndrome which is characterised by neurological symptoms from rapid decreases in peripheral osmolality. As the osmolality decreases, cerebral oedema occurs leading to an increase in intracranial hypertension (ICH).   Symptoms can range from vomiting and lethargy to more severe signs including seizures, obtundation and cardiac dysrhythmias. Should neurological signs occur, administration of a hyperosmolar osmotic agent (mannitol/hypertonic saline) is recommended for the ICH. Ideally one would also slow the decrease in osmotically active solutes (BUN in particular) although this can be difficult to achieve in these patients. 

Recurrence

In general, recurrence rates are anywhere between 20-45% in the first few months post-obstruction. Factors that may affect recurrence include the use of a 5fr urethral catheter and use of phenoxybenzamine but not the duration of catheterisation, administration of antimicrobials, use of pain medications or presence of an infection at admission. Independently, only increasing dietary water content was associated with decreased recurrence.

[S Jasani: the emphasis in this paragraph on recurrence should very much be on ‘…that MAY affect recurrence’. While Lisa kindly gives up her time to write these blogs posts, she is not able to simultaneously provide full evidence-based medicine critiques of the references listed. Type of study, methodology, sample size, size of any effect reported, etc. all need to be considered before drawing conclusions that may affect your personal clinical practice.]

References:

Kruger, J.M., Conway, T.S., Kaneene, J.B., Perry, R.L., Hagenlocker, E., Golombek, A. and Stuhler, J., 2003. Randomized controlled trial of the efficacy of short-term amitriptyline administration for treatment of acute, nonobstructive, idiopathic lower urinary tract disease in cats. Journal of the American Veterinary Medical Association, 222(6), pp.749-758.

Ostroski, C.J. and Cooper, E.S., 2014. Development of dialysis disequilibrium‐like clinical signs during postobstructive management of feline urethral obstruction. Journal of veterinary emergency and critical care, 24(4), pp.444-449.

Hetrick, P.F. and Davidow, E.B., 2013. Initial treatment factors associated with feline urethral obstruction recurrence rate: 192 cases (2004–2010). Journal of the American Veterinary Medical Association, 243(4), pp.512-519.

Cooper, E.S., 2015. Controversies in the management of feline urethral obstruction. Journal of Veterinary Emergency and Critical Care, 25(1), pp.130-137.

Reineke, E.L., Thomas, E.K., Syring, R.S., Savini, J. and Drobatz, K.J., 2017. The effect of prazosin on outcome in feline urethral obstruction. Journal of Veterinary Emergency and Critical Care.

Dorsch, R., Zellner, F., Schulz, B., Sauter-Louis, C. and Hartmann, K., 2016. Evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis. Journal of feline medicine and surgery, 18(11), pp.925-933.

Osborne, C.A., Kruger, J.M., Lulich, J.P., Johnston, G.R., Polzin, D.J., Ulrich, L.K. and Sanna, J., 1996. Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study. Veterinary Clinics: Small Animal Practice, 26(3), pp.563-569.

Delille, M., Fröhlich, L., Müller, R.S., Hartmann, K. and Dorsch, R., 2016. Efficacy of intravesical pentosan polysulfate sodium in cats with obstructive feline idiopathic cystitis. Journal of feline medicine and surgery, 18(6), pp.492-500.

Francis, B.J., Wells, R.J., Rao, S. and Hackett, T.B., 2010. Retrospective study to characterize post-obstructive diuresis in cats with urethral obstruction. Journal of feline medicine and surgery, 12(8), pp.606-608.

Anaphylaxis Refresher

By Lisa Murphy DACVECC

Overview 

Anaphylaxis is a common presenting complaint in small animal practice that requires prompt recognition and treatment for a successful outcome. Common definitions of anaphylaxis include:

“A severe, potentially fatal, systemic, immediate hypersensitivity reaction most commonly caused by the IgE-mediated immunologic release of mediators from mast cells and basophils”. 

Types

There are several categories of anaphylactic reactions although the clinical signs are similar and difficult to differentiate between each type:

  1. Immunologic IgE-mediated (e.g. insect stings, reptile venom, food, medications)
  2. Immunologic non-IgE mediated (e.g. IV immunoglobulins) 
  3. Non-immunologic (cold, water, exposure, some chemotherapeutic agents)

The classic pathway for anaphylaxis involves initial exposure to an antigen resulting in sensitization of mast cells. Repeat antigen exposure leads to the release of IgE, activation of mast cells, and release of multiple mediators including histamine, heparin, tryptase, kallikreins, proteases and proteoglycans among others. These mediators lead to vascular permeability and vasodilation which cause hypotension and other signs.

Clinical Signs

Clinical signs of anaphylaxis can vary with different species. In general the more rapid the signs the more severe the symptoms. In dogs, common manifestations include dermal and gastrointestinal signs; respiratory distress is more common in cats.

  • Dermal: erythema, urticaria, angioedema 
  • Gastrointestinal: nausea, vomiting, diarrhoea
  • Cardiovascular: tachycardia, hypotension, dysrhythmia
  • Respiratory: nasal congestion, stridor, dyspnea, bronchospasm, tachypnea 
  • Neurologic: weakness, seizures 
  • Ocular: pruritis, lacrimation 
A cat with anaphylaxis (Lisa Murphy)

A cat with anaphylaxis (Lisa Murphy)

Lily

Let’s meet Lily who is a 4-year old female spayed Yorkshire terrier (5 Kg). She presented with acute onset collapse after a walk. Soon after she developed vomiting and diarrhoea and became minimally responsive. Lily’s carers had witnessed her ingesting a bee. 

Physical exam findings: 

Major systems (primary survey)

  • Cardiovascular:
    • Heart rate: 160 bpm
    • Mucous membranes: light pink, CRT 1sec 
    • No murmur, tachycardic with poor femoral pulses
  • Respiratory:
    • Rate > 60 breath per minute with increased effort, stridorous 
    • Thoracic auscultation: increased bronchovesicular sounds bilaterally
  • Neurological:
    • Dull mentation, non-ambulatory x4

Secondary survey:

  • Temp 36.6⁰/98.0F
  • Abdominal palpation: soft, not distended
  • Rectal: diarrhoea, hematochezia 

Diagnostics

Minimum and extended database as indicated and routine for emergency patients.

Full blood work is recommended at the appropriate time for patients with severe anaphylaxis.
Potential changes include:

  • Elevations in liver enzymes (especially ALT)
  • Azotemia (pre-renal or renal)
  • Hemoconcentration
  • Coagulopathy
  • Thrombocytopenia

Thoracic radiographs are non-specific. In dyspneic animals, they may show an interstitial or alveolar lung pattern and/or microcardia.

If available, abdominal ultrasonography can be used to evaluate the gallbladder in dogs. One reference suggests that gallbladder wall edema may be over 90% specific for anaphylaxis secondary to hepatic venous congestion (Quantz et al, 2009). There are no studies evaluating if this occurs in cats.

 
Gallbladder wall edema in a dog (Lisa Murphy)

Gallbladder wall edema in a dog (Lisa Murphy)

 

Diagnostics were performed on Lily which revealed the following abnormalities:

Hematology:

  • Hematocrit (HCT) 60% (35-55%)
  • White blood cell count (WBCC) 16,500 (5000-16,700)
  • Platelets 100,000 (148,000-480,000)

Chemistry:

  • ALT 500 (10-125)
  • ALP 350 (23-212)
  • Total bilirubin (Tbili) 0.5 (0.1-0.6)
  • BUN 80 mg/dL (5-35) [28.57 mmol/L (1.79-12.5)]
  • Creatinine 3.0 (0.5-1.8) [265.26 umol/L (44.21-159.16)]
  • Glucose 56 mg/dL (80-150) [3.1 mmol/L (4.44-8.33)]

Thoracic radiographs: no cardiomegaly, mild bronchointerstitial pattern
Point of care ultrasound:

  • Abdominal: no ascites, gallbladder wall edema suspected
  • Thoracic: no free fluid 

Blood pressure (via non-invasive Doppler): 50 mmHg 

Considering the above diagnostics and Lily’s physical exam findings, her problem list could include the following:

  • Shock
  • Dyspnea
  • Hypotension
  • Vomiting, diarrhoea
  • Hypoglycemia
  • Elevated liver enzymes
  • Azotemia
  • Hemoconcentration
  • Dull mentation

Treatment

There are several treatment options for anaphylaxis but few are well-supported by evidence of significant patient benefit. Many of the problems treating anaphylaxis stem from the fact the signs are secondary to multiple mediators, not just histamine.

The hypotension seen in severe anaphylaxis should be addressed with appropriate fluid resuscitation – 90ml/kg in dogs, 60ml/kg in cats, given in aliquots with a constant reassessment of the patient’s clinical signs.

However fluid therapy alone is not sufficient in severe cases.

Epinephrine (adrenaline): 

This is a first-line treatment and the only medication that has proven a benefit. It is typically reserved for severe cases.

  • Benefits of administration include a reduction in the further release of histamine and other anaphylactic mediators from mast cells; and, increased cardiac output via cardiac β1 adrenergic effects and vasoconstriction via α1 vascular effects.
  • Side effects following rapid administration include tachycardia, tremors and anxiety
  • Route of administration: continuous intravenous infusion is the preferred route of treatment in cases of severe anaphylaxis. Subcutaneous dosing should be avoided due to unpredictable effects and delayed absorption via the skin in these patients.

Dose/route:

  • 2.5-5mcg/kg IV, 10mcg/kg IM
  • 0.05mcg/kg/min IV via CRI

Other therapies:

Antihistamines: 

Histamine concentrations peak at the onset of anaphylaxis but quickly return to normal
Little evidence supports the use of pre-treatment with anti-histamines to prevent anaphylaxis although they are a very well tolerated medication
Antihistamines can be effective for localized/dermal allergic reactions and may reduce gastric acid secretion

Diphenhydramine: 2-4mg/kg IM, PO q 8-12h
Ranitidine:

  • 2mg/kg PO q8-12h (dogs)
  • 3.5mg/kg PO q 12h (cats)

Glucocorticoids:

Due to the delayed onset of their beneficial effects (typically 4-6 hours after administration) they are not considered a first line drug
Benefits lie in the downregulation of the late eosinophilic inflammatory response preventing biphasic anaphylaxis
Pre-treatment with glucocorticoids will be unlikely to prevent anaphylaxis and could theoretically blunt the physiologic response
Dexamethasone: 0.1-0.5mg/kg IV

Bronchodilators:

Selective β2 adrenergic agonists (e.g. albuterol 90mcg per actuation for inhalation) when given via an inhaled route, may be beneficial to control respiratory signs of anaphylaxis
These medications cannot replace epinephrine as they have no effects on β1 or α1 receptors
Side effects: tachycardia, tremors 

A possible treatment plan for Lily may include the following:

  • Placement of an intravenous catheter
  • Administration of 10-20ml/kg of crystalloid as a bolus followed by reassessment of her perfusion parameters; additional boluses given as indicated.
  • Administration of epinephrine (adrenaline) 5mcg/kg IV bolus if she remains hypoperfused
  • Consideration for diphenhydramine 2m/kg IM and Dexamethasone 0.1mg/kg IV 

EpiPen:

Many carers will inquire about use of an EpiPen which people with hypersensitivities commonly carry. This is of most benefit for acute bronchospasm and upper airway edema. These are uncommon in canine cases of anaphylaxis so it may not be of much benefit to our patients.

The other major issue is dosing. The adult EpiPen contains 0.3mg of epinephrine (adrenaline) which would only be safe in animals weighing > 30 Kg); EpiPen Junior contains 0.15mg which could be used in animals between 15-30 Kg.

Finally, pet carers should be reminded that any animal treated with an EpiPen should still be seen by a veterinarian as soon as possible.

Feel free to contact me with comments or questions. Write them below or email me at lisamurphyirish@gmail.com. 

References: 

Shmuel, D.L. and Cortes, Y., 2013. Anaphylaxis in dogs and cats. Journal of Veterinary Emergency and Critical Care, 23(4), pp.377-394.

Walters, A.M., O'Brien, M.A., Selmic, L.E. and McMichael, M.A., 2017. Comparison of clinical findings between dogs with suspected anaphylaxis and dogs with confirmed sepsis. Journal of the American Veterinary Medical Association, 251(6), pp.681-688.

Aharon, M.A., Prittie, J.E. and Buriko, K., 2017. A review of associated controversies surrounding glucocorticoid use in veterinary emergency and critical care. Journal of Veterinary Emergency and Critical Care, 27(3), pp.267-277.

Mink, S.N., Simons, F.E.R., Simons, K.J., Becker, A.B. and Duke, K., 2004. Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs. Clinical & Experimental Allergy, 34(11), pp.1776-1783.

Silverstein, D. and Hopper, K., 2014. Small Animal Critical Care Medicine. Elsevier Health Sciences.

Quantz, J.E., Miles, M.S., Reed, A.L. and White, G.A., 2009. Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients. Journal of veterinary emergency and critical care, 19(6), pp.536-544.