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.