This page is for adult patients. For pediatric patients, see:Anaphylaxis (peds).


  • Type I hypersensitivity reaction that is either severe in nature or having two or more organ systems involved.
  • Clinically Anaphylaxis and its treatment is virtually identical whether it is the traditional IgE dependent anaphylaxis reaction (vast majority), or the IgE independent anaphylactoid reaction
  • Precipitants
    • Food (most common)
    • Medications
    • Insect stings
    • Latex
    • Aerobic exercise
    • Idiopathic (rare)

Clinical Features

Raised urticaria
Angioedema of tongue
Angioedema of face.
  • Cutaneous symptoms (90%)
  • Respiratory symptoms (70%)
  • Gastrointestinal symptoms (40%)
    • Abdominal pain
    • Nausea, vomiting
    • Diarrhea
  • Cardiovascular symptoms (35%)
  • Central Nervous System
    • Uneasiness
    • Altered mental status
    • Headache, dizziness, confusion
    • Syncope

Expected Course

Uniphasic (80-90%)

  • Symptoms peak within 30 minutes to 1 hour after onset, resolve within 30 minutes to 1 hour of receiving treatment[1]

Biphasic (10-20%)

Biphasic reactions are rare and can occur anywhere from 10 minutes up to six days after an initial reaction.[2]

  • Uniphasic response, followed by asymptomatic period of hour or more, then return of symptoms
  • The second phase does not necessarily resemble the first!
  • More likely with a severe initial presentation or repeated epinephrine doses. Additionally hypotension, widened pulse pressure, unknown trigger, and drug trigger in children[3][4]
  • Little evidence to support the use of discharge steroids to prevent a biphasic reaction
  • 0.4% of patients with anaphylaxis had a rebound event while in the ED[5]

Differential Diagnosis

Acute allergic reaction


Erythematous rash


Anaphylaxis is highly likely when ANY ONE of the following criteria is fulfilled[6][7]

Criterion 1 (90% of patients)

  • Acute onset of an illness involving the skin, mucosal tissue, or both AND at least one of the following:
    • Respiratory Compromise
    • Reduced blood pressure or associated symptoms (Syncope, Dizziness)

Criterion 2 (10-20% of patients)

  • TWO OR MORE of the following that occur rapidly after exposure to a LIKELY allergen for that patient
    • Involvement of the skin-mucosal tissue (hives, swollen lips-tongue-uvula)
    • Respiratory compromise
    • Hypotension or associated symptoms
    • Persistent gastrointestinal symptoms: (vomiting, diarrhea, crampy abdominal pain)

Criterion 3

  • Hypotension after exposure to a KNOWN allergy for that patient (minutes to hours):
    • Adults: systolic blood pressure (SBP) <90 mmHg or >30% reduction from baseline
    • Pediatrics
      • 1 month - 1 year: SBP <70 mmHg
      • 1 year - 10 years: SBP <(70 mmHg + [2 x age])
      • 11 years - 17 years: SBP <90 mmHg


  • Epinephrine
    • 1:1000 IM 0.3 - 0.5mg (0.3 - 0.5mL) every 5 - 15 minutes[8][9]
    • Give as soon as possible
    • Always IM initially [10]
    • If response to IM is inadequate: give epinephrine infusion 1:10,000 2 - 10 µg/min
    • How to make a quick epinephrine drip: Take your code-cart epinephrine (it does not matter if it is 1:1,000 or 1:10,000) and inject 1mg into a liter bag of NS. Final concentration is 1mcg/ml. Run at 1cc/min and titrate to effect.
  • Pediatric: Epinephrine 1:1000 0.01mg/kg (max 0.5mg) IM every 5 to 15 minutes
    • IV infusion: 0.05 - 1 mcg/kg/min
  • Supplemental oxygen
  • Normal saline bolus
    • If unresponsive to epinephrine assume distributive shock and give 1 - 2 liters of normal saline
  • Also consider
    • Albuterol for bronchospasm resistant to IM epinephrine
    • Antihistamines (for symptom control AFTER hemodynamically stable)
      • Diphenhydramine: 25 to 50mg IV (1mg/kg in children)
      • Ranitidine: 50mg IV (0.5mg/kg in children) (has been found to improve urticaria but not angioedema at 2 hours[11])
      • AVOID promethazine as this can worsen hypotension
    • Glucocorticoid
      • MAY blunt biphasic reaction although little evidence to support usage[12]
      • Methylprednisolone: 125mg IV (2mg/kg in children)
      • Dexamethasone: 10mg IV or PO (0.6mg/kg in children)
    • Glucagon
      • 1 - 5mg IV over 5 minutes followed by infusion of 5 - 15 µg/min[13]
      • If taking beta-blocker AND unresponsive to epinephrine
    • Consider adding additional pressor support if persistent hypotension present



  • Severe and moderate presentations, especially if symptoms did not respond promptly to epinephrine or required repeat dosing
  • Labs that may be requested by allergist/admitting team if uncertain diagnosis
    • Histamine level - serum elevation 30-60 min following anaphylaxis, window easily missed
    • Tryptase - peaks at 2-4 hrs, remains elevated 6-12 hrs


  • Consider discharge after 1 hour observation, if no severe symptoms and no repeat epinephrine doses (AAAAI recommendations)[4]
    • NPV of 1-hour observation was 95%, with NPV for biphasic anaphylaxis after >6 hours of observation of 97.3% [16]
  • Send home with an epinephrine autoinjector! (Epi-Pen)
    • Up to 6% of the people with anaphylaxis have a repeat ED visit for anaphylaxis within 7 days[5]

See Also

External Links


  1. Ewan PW. ABC of allergies – Anaphylaxis, BMJ 1998; 316: 1442-1445
  2. Milne K. Biphasic Allergic Reactions: Observation, Treatment Guidelines
  3. Ellis AK, Day JH: Incidence and characteristics of biphasic anaphylaxis: A prospective evaluation of 103 patients. Ann Allergy Asthma Immunology. 2007; 98:64-69
  4. 4.0 4.1 Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020; 145:1082.
  5. 5.0 5.1 Grunau BE et al. Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients With Allergic Reactions or Anaphylaxis. Ann Emerg Med. 2013 Nov 13
  6. Brown SGA, Mullins RJ and Gold MS. Anaphylaxis: diagnosis and management, MJA 2006; 185: 283–289
  7. Lieberman P et al. The diagnosis and management of anaphyalxis: An updated practice parameter, J Allergy Clin Immunol 2005;115;3:S483-S523
  8. Dhami S. et al. Management of anaphylaxis: a systematic review. Allergy. 69 (2014) 168–175.
  9. Sheikh A, Shehata YA, Brown SGA, Simons FER. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006312. DOI:10.1002/14651858.CD006312.pub2
  10. Simons FER, Gu X, Simons KJ. Epinephrineabsorption in adults: Intramuscular versus subcutaneous injection, J Allergy Clin Immunol 2001;108:871-3
  11. Lin, RY et al. Improved Outcomes in Patients With Acute Allergic Syndromes Who Are Treated With Combined H1 and H2 Antagonists. Annals of Emergency Medicine. 36:5 NOVEMBER 2000.
  12. Choo KJ, Simons E, Sheikh A: Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65:1205-1211.
  13. Campbell RL, et al. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014; 113:599e608.
  14. Schummer et al. The Pivotal Role of Vasopressin in Refractory Anaphylactic Shock. Anesthesia & Analgesia: August 2008 - Volume 107 - Issue 2 - pp 620-624.
  15. Dünser et al. Treatment of Anaphylactic Shock: Where Is the Evidence? Anesthesia & Analgesia: August 2008 - Volume 107 - Issue 2 - pp 359-361
  16. Shaker M, Wallace D, Golden DBK, Oppenheimer J, Greenhawt M. Simulation of health and economic benefits of extended observation of resolved anaphylaxis. JAMA Netw Open 2019;2:e1913951.