• Anaphylaxis is a potentially life-threatening emergency that requires immediate diagnosis and treatment.
• The exact incidence of anaphylaxis is not known, but recent evidence suggests that it is increasing.
• There are approximately 1500 fatal cases of anaphylaxis in the United States per year.
• Anaphylaxis presents with a sudden onset of signs and symptoms, usually in more than one body system, within minutes to hours of exposure to a trigger.

Anaphylaxis is a clinical diagnosis and is highly likely when any one of the following three criteria is filled:

1. Sudden onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (ie. generalized hives, itching or flushing, swollen lips-tongue-uvula) and at least one of the following:
   • Respiratory compromise (ie. shortness of breath, wheeze, cough stridor, hypoxemia).
   • Reduced BP or associated symptoms of end-organ dysfunction (ie. hypotonia [collapse], syncope, incontinence).

2. Two or more of the following occurring rapidly (minutes to several hours) after exposure to a likely allergen or other trigger for that patient:
   1. Involvement of the skin-mucosal tissue (ie. generalized hives, itch-flush, swollen lips-tongue-uvula).
   2. Sudden respiratory compromise (ie. shortness of breath, wheeze, cough, stridor, hypoxemia).
   3. Sudden reduced BP or symptoms of end-organ dysfunction (ie. hypotonia [collapse], syncope, incontinence).
   4. Sudden gastrointestinal symptoms (ie. crampy abdominal pain, vomiting).

3. Reduced BP after exposure to a known allergen for that patient (minutes to several hours):
   1. Infants and children: Low systolic BP (age specific) or greater than 30% decrease in systolic BP.
   2. Adults: Systolic BP of less than 90 mm Hg or greater than 30% decrease from baseline.

Clinical Presentation

• Anaphylactic reactions often present as a combination of clinical characteristics, commonly affecting an array of organ systems:
  • Skin (80% to 90% of episodes)
  • Respiratory tract (70% of episodes)
  • Gastrointestinal tract (30% to 45% of episodes)
  • Cardiovascular (10% to 45% of episodes)
  • Central nervous system (10% to 15% of episodes)
• Nasal congestion, sneezing, ocular itching, and tearing are also common complaints.
• Patients with laryngeal edema often complain of hoarseness, throat tightness, or stridor.
• Death from anaphylaxis usually results from asphyxiation due to upper or lower airway obstruction, or from cardiovascular collapse.

• Prompt assessment and treatment are critical in anaphylaxis, as respiratory or cardiac arrest and death can occur within minutes.
• The literature has shown that early administration of epinephrine improves patient outcomes and decreases the likelihood of death.
• Initial management:
  • If applicable, remove the inciting cause (ie. stop infusion of a suspect medication).
  • Administer epinephrine as early as possible.
    • 0.3-0.5 mg IM, repeat every 5-15 minutes PRN.
  • Consider and prepare for intubation.
    • Airway edema can rapidly obscure visualization of the cords and necessitate a surgical airway.
    • Intubate early if airway compromise is present.
  • Basics: ABCs, obtain two large-bore IV catheters, initiate supplemental oxygen at 8-10 LPM via nasal prongs, place patient on cardiac monitors.
  • Fluid resuscitation with 1-2 litres of normal saline rapid bolus.
  • Place patient in recumbent position with lower extremities elevated.
• Anaphylaxis refractory to IM epinephrine:
  • Start IV epinephrine drip at 1-5 mcg/min and titrate (use IV epinephrine with caution as dosing errors can cause myocardial ischemia/infarction).
  • The addition of another vasopressor should be considered if the patient continues to be hypotensive despite maximal epinephrine and fluid resuscitation.
  • Few case reports support the use of methylene blue, an inhibitor of nitric oxide synthase and guanylate cyclase.
    • The efficacy and ideal dose of methylene blue is unknown, but a single bolus of 1 to 2 mg/kg given over 20 to 60 minutes has been used in cardiac surgery.
  • Extracorporeal membrane oxygenation (ECMO): The decision to initiate ECMO should be considered early in patients unresponsive to traditional resuscitative measures, before irreversible ischemic acidosis develops.

Adjunctive Treatments (non-lifesaving)

• Epinephrine is first-line treatment for anaphylaxis, and there is no known equivalent substitute.
• None of these medications should be used as the initial treatment or as the sole treatment, because they do not relieve upper or lower respiratory tract obstruction, hypotension, or shock:
  • H1 antihistamines: ie. diphenhydramine 25-50 mg IV over 5 minutes q4-6 hours PRN (maximum dose of 400 mg per 24 hours).
  • H2 antihistamines: ie. famotidine 20 mg IV over at least 2 minutes.
  • Bronchodilators: ie. nebulized salbutamol.
  • Corticosteroids: ie. IV methylprednisolone.

Special Considerations

• Beta blockers: thought to be associated with higher risk for severe anaphylaxis.
  • Give glucagon 1-5 mg IV administered over 5 minutes, followed by an infusion of 5-15 mcg/min in patients on beta-blockers with refractory anaphylaxis.
• Monoamine oxidase inhibitors and tricyclic antidepressants: extend the duration of action of epinephrine.

• Dependent on resource availability.

• All patients with suspected anaphylaxis should be closely monitored as above.
• Additional help should be called as needed (ie. involvement of ICU, anesthesia).

• All patients with anaphylaxis should be observed until symptoms have completely resolved.
• Admission or observation is recommended for patients who do not respond promptly to IM epinephrine, require >1 dose of epinephrine, or received epinephrine only after a significant delay (>60 minutes), as these features may be risk factors for a biphasic response.
• All patients should be sent home with:
  • An anaphylaxis emergency plan.
  • At least one epinephrine auto-injector or a prescription for two epinephrine auto-injectors.
  • Printed information about anaphylaxis and its treatment.
  • Documented advice to follow up with an allergist, with a referral if possible.

1. Simons, F. E., Ardusso, L. E., Bilò, M. B., Dimov, V., Ebisawa, M., El-Gamal, Y. M., & Worm, M. (2012). 2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Current Opinion in Allergy and Immunology, 12(4):389-99.

   
   

2. Campbell, R.L., Li, J.T., Nicklas, R.A., & Sadosty, A. (2014). Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Annals of Allergy, Asthma and Immunology, 113(6):599-608.

   
   

3. Sheikh, A., Shehata, Y.A., Brown, S.G., & Simons, F.E. (2009). Adrenaline for the treatment of anaphylaxis: cochrane systematic review. Allergy, 64(2):204.

   
   

4. Sampson, H.A., Mendelson, L., & Rosen, J.P. (1992). Fatal and near-fatal anaphylactic reactions to food in children and adolescents. New England Journal of Medicine, 327(6):380.

   
   

5. White, J.L., Greger, K.C., Lee, S., Kahoud, R.J., Li, J.T., Lohse, C.M., & Campbell, R.L. (2018). Patients taking beta-blockers do not require increased doses of epinephrine for anaphylaxis. Journal of Allergy and Clinical Immunology: In Practice, 6(5):1553.

   
   

6. Thomas, M., & Crawford, I. (2015). Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta-blockers. Emergency Medicine Journal, 22(4):272.

   
   

7. UpToDate: Anaphylaxis: Emergency treatment.

   
   

8. Rosen’s Emergency Medicine: Concepts and Clinical Practice, Chapter 109, 1418-1429.e2 (Allergy, Hypersensitivity & Anaphylaxis).