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.