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Rebound Anaphylaxis

Mike Weinstock, MD, Anand Swaminathan, MD, and Mizuho Morrison, DO

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Discuss need for prolonged observation to monitor for rebound, after epinephrine administration in anaphylaxis.


  • After giving epinephrine for an anaphylactic reaction, 6 full hours of observation is likely unnecessary and 2-3 hours is probably sufficient.

  • The timing of a rebound anaphylactic reaction is unpredictable.

  • Strict return precautions are critical and consider how easily and quickly a patient can get back to you when deciding how long to observe.

  • A patient who receives epinephrine for an allergic reaction in the Urgent Care MUST be discharged with an Epi-Pen.



  • Patients with an allergic reaction that involves any compromise to their ABCs.  

    • Airway: full sensation in the throat? give it

    • Breathing: wheezing? give it

    • Circulation: soft blood pressure? give it



  • Relative contraindications listed are:

    • Coronary artery disease

    • Hypertension

    • Tachycardia

  • However, in patients with anaphylaxis there is no contraindication to epinephrine.  If they cannot get oxygen, it does not matter if they have CAD or not.  Without oxygen, the heart dies.

  • Cydulka R, et al. The use of epinephrine in the treatment of older adult asthmatics. Ann Emerg Med. 1988 Apr;17(4):322-6. [PMID: 3354935]

    • Gave epinephrine to patients between 15 and 96 for asthma (before we had beta-agonists).  No one had an ischemic event or a lethal dysrhythmia.

  • Allergy to epinephrine?

    • Patients who have a reported allergy to epinephrine are allergic to the diluent.  There is another form of epinephrine that has an different diluent, but it is never available to you.

    • This is very, very rare.



  • We are traditionally taught that patients need to be observed for 4-6 hours after administration of epinephrine for an anaphylactic reaction.

  • The observation period is necessary because there is a risk of a rebound anaphylaxis that can occur after the epinephrine has worn off. There is not a lot of evidence to tell us the true time frame and risk of rebound anaphylaxis.  

  • Early studies described a 30% risk of rebound, but they included any recurrent symptoms as rebound, including hives or pruritis.  

  • What we actually care about is which patients had recurrence of shortness of breath, hypotension or airway swelling. These are severe biphasic reactions that are very rare.

  • Grunau BE, et al. Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. Ann Emerg Med 2014 Jun; 63:736. [PMID 24239340]

    • Looked at a large registry of patients with anaphylactic reactions in Canada where patients have very good follow up.  

    • 5 patients in the study had a recurrent, biphasic anaphylactic reaction.  This is a rate of 0.18%.  

    • One of these biphasic reactions occurred 6 days after the initial reaction.   


  • In summary, the severe reaction is rare, and can occur very late. Your discharge instructions need to be clear and are more important than how long the patient is observed in the Urgent Care.  

  • Remember: if you give epinephrine for an allergic reaction, you must discharge them with an epi-pen to go home with and tell them how to use it.  

Anita O. -

Thanks for the answer, and for the shout out!!! Anita O'Malley PA

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Cross-React and HACK Full episode audio for MD edition 209:41 min - 98 MB - M4Ahippo Urgent Care RAP - October 2016 479 KB - PDF