Refractory anaphylaxis: Treatment algorithm

Abstract

There is no established definition for refractory anaphylaxis. The European Anaphylaxis Registry use a definition of "anaphylaxis which, despite treatment with at least two doses of minimum 300 μg adrenaline, does not achieve normalization" of symptoms. 1 A US-based panel recently proposed a reaction which "must be treated with 3+ appropriate doses of epinephrine (or initiation of an intravenous epinephrine infusion)" 2 -a definition which does not specifically refer to treatment response, although this is implied. The Resuscitation Council UK (RCUK) recently updated its guideline on the emergency treatment of anaphylaxis, defining refractory anaphylaxis as a reaction "requiring ongoing treatment despite two (appropriate) doses of intramuscular adrenaline" and proposes an algorithm to facilitate management (Figure 1). 3Refractory anaphylaxis is rare: the European Registry reported a rate of 0.37% of all anaphylaxis cases reported in the registry, with

Grading the severity of anaphylaxis

“…(1) Lack of granularity due to a limited number of categories (2) Non-specific terminology and lack of definition over certain symptoms. (3) Nonequivalency of symptoms/signs, for example, dyspnea and shock sometimes included as equivalent symptoms in the same severity grade (4) Some grading systems base severity on the number of organ systems involved, but severe reactions can occur with only single-organ involvement (5) Use of treatment (e.g., epinephrine) is a poor indicator of severity (6) Using symptom duration to guide severity is challenging (7) Some grading systems include different degrees of severity within each organ system, but do not account for the totality of symptoms when assessing overall severity However, some of these considerations are debatable: for example, while any epinephrine use is a poor indicator of severity, a need for multiple doses of epinephrine due to suboptimal response is arguably a useful indicator of refractory reactions [28,29].…”

“…Complicating this objective with assignment of a severity grade is not only unnecessary, but might even delay treatment and thus cause harm. In this light, using a sub-optimal response to two doses of epinephrine could be a useful indicator of refractory anaphylaxis and the need to escalate clinical treatment [28,29,46].…”

Emergency treatment of anaphylaxis: concise clinical guidance

“…There is no established definition of refractory anaphylaxis, so the RCUK has defined it as 'anaphylaxis requiring ongoing treatment (due to persisting respiratory or cardiovascular symptoms) despite two appropriate doses of IM adrenaline.' 1,43 A systematic review and meta-analysis found an estimated 3.4% of adrenaline-treated reactions have a suboptimal response to two doses of adrenaline, although most respond to three. 14 Early recognition is vital, and critical care support should be sought early.…”

“…Intravenous fluid infusion is, therefore, crucial to treat shock and provide sufficient circulating volume to maintain cardiac output and deliver adrenaline at the tissue level. 43 In cases where the ABC features of anaphylaxis persist despite two doses of IM adrenaline, a low-dose adrenaline infusion is likely to be much more effective than IM or IV boluses. [46][47][48] As such, this along with fluid resuscitation form the basis of treatment in the 2021 guideline.…”

Improving the reporting of allergic adverse events during immunotherapy for food allergy

“…3 This cutoff is also consistent with data from the European Anaphylaxis Registry and at least 1 national guideline. 4 Wider discussion is needed to achieve consensus (with due consideration of published data sets), because limiting grade 4 reactions to those in whom 41 epinephrine doses are given might be too restrictive. Although this schema is not designed to guide treatment, we also suggest intramuscular epinephrine should be listed as the treatment for grade 4 reactions (rather than the current text, which might imply other bronchodilators can be used as first-line treatment).…”