UMEM Educational Pearls

Refractory Anaphylaxis

  • Refractory anaphylaxis is defined as anaphylaxis that does not respond to at least 2 doses of 300 mcg of epinephrine given IM into the anterolateral thigh.
  • Refractory anaphylaxis can be due to several factors including patient comorbidities, delayed diagnosis, delayed epinephrine administration, or concomitant beta-blocker or ACE-inhibitor medication use.
  • Consider the following treatments in patients with refractory anaphylaxis, persistent hypotension, and shock:
    • Aggressive IVF resuscitation - patients may need up to 7L of IVFs
    • Epinephrine infusion (1-10 mcg/min) to target a MAP of 65 mm Hg
    • Glucagon (1-5 mg via slow IV push) for those taking a beta-blocker and who fail to respond to epinephrine
    • Norepinephrine, vasopressin, angiotensin II, methylene blue, or dobutamine can be administered with epinephrine for persistent hypotension. 
    • VA-ECMO - though there is no prospective evidence on the use of ECMO in anaphylaxis.


Krishnaswamy G. Critical care management of anaphylaxis: A conside definitive review. Crit Care Med. 2021.