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Our patient:

27 y/o M patient, went to eat at a new restaurant, now having facial swelling and shortness of breath, rash.

What makes Anaphylaxis?

- Severe, life-threatening allergic reaction

- Sudden onset of signs/symptoms

- Involving MORE THAN ONE body system

Our patient got 0.3mg IM Epinephrine

He feels much better. Now what? Do we observe for 3 hours, 4 hours? 6 hours?

What do we do now?

Biphasic Anaphylaxis - it's what we are worried about!

- Subsequent onset of anaphylaxis symptoms after treatment of initial phase of symptoms

- Doesn't necessarily resemble first phase!

- Traditional teaching is to observe patients for 4-6 hours after resolution of symptoms with IM Epi

- My Question: Is the 4-6h observation period after giving someone ONE DOSE of IM epi necessary if patient experiences complete resolution of symptoms?

Note: does not apply to patients recieving multiple doses of epi - these should be considered for admission

Our patient obviously has more than one sign of organ involvement that occurred minutes after ingesting what he thought was a safe food at the restaurant - anaphylaxis

Secure the airway, remove inciting cause ( if needed), and GIVE THE EPINEPHRINE

- 0.3 - 0.5mg IM in lateral thigh (0.01 mg/kg in child - max 0.3mg)

- Infusion for inadequate treatment ( 1mcg/kg/min) if necessary, consider glucagon, pressors, etc

- Adjuncts: IV NS, albuterol, antihistamines, glucocorticoid

How often does it occur?

Spoiler alert: Not too often, but estimates range from .1% - 20%

Why the variability?

Older, smaller retrospective studies reported incidences of biphasic reactions as high as 21%. However, larger more recent studies have reported the incidence to be much lower, around 4–4.5% (Pourmand et al - 2018)

Lee et al - Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis (2015)

- 4114 patients from 27 observational studies with anaphylaxis - 192 with biphasic reactions (4.6%)

Kraft et al - Risk Factors and Characteristics of Biphasic Anaphylaxis (2020)

- Data from Anaphylaxis Registry (11 countries), 8736 patients with anaphylaxis - rate of biphasic reaction was 4.7%, or 435 patients

- The type of study vastly alters the outcome...

- Are they only reporting clinically significant biphasic reactions? What does this mean?

- What clinical setting is this? What is causing the anaphylaxis?

Overall?

Biphasic anaphylaxis is rare, but incidence overall is unclear.

Most biphasic reactions will likely fall outside a 4-6h observation window

Medicine is not an algorithm - you can use your clinical judgement to determine who may need to stay for observation

When in doubt, give epinephrine as soon as possible

After how long can you expect it to happen?

Spoiler again: we aren't sure. 1-72h?

Sources

Times vary. Studies report onset of second phase of biphasic reaction from 1-72 hours

- Pourmand et al did meta analysis of 16 studies, found mean time of onset to be >8h (2018)

- Kraft et al did meta analysis of 435 biphasic reactions in Anaaphylaxis Registry and found 60% occurred within 12 hours, another 24% between 12-24h, and 15% after 24h.

- Lee et al did meta analysis of 192 patients from 27 observational studies with biphasic reactions - mean time of onset was 11 hours

All of these are outside of the recommended window

How about steroids ??

- There appears to be no benefit to administering corticosteroids in preventing BA

- Few papers appear to show potential increased risk of admissions and severe reactions

Pourmand, Ali, et al. “Biphasic Anaphylaxis: A Review of the Literature and Implications for Emergency Management.” The American Journal of Emergency Medicine, vol. 36, no. 8, 2018, pp. 1480–1485., https://doi.org/10.1016/j.ajem.2018.05.009.

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

Biphasic anaphylaxis: A review of the literature and implications for emergency management. Pourmand A, Robinson C, Syed W, Mazer-Amirshahi M. Am J Emerg Med. 2018;36(8):1480. Epub 2018 May 9.

Shaker MS 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(4):1082. Epub 2020 Jan 28.

Kraft, Magdalena. “Risk Factors and Characteristics of Biphasic Anaphylaxis .” Journal of Allergy and Clinical Immunology, vol. 8, no. 10, Nov. 2020, pp. 3388–3395.

Alqurashi, W. (2020). Biphasic Anaphylaxis: Epidemiology, Predictors, and Management. In: Ellis, A. (eds) Anaphylaxis. Springer, Cham. https://doi.org/10.1007/978-3-030-43205-8_4

Gabrielli S, Clarke A, Morris J, Eisman H, Gravel J, Enarson P, et al. Evaluation of prehospital

management in a Canadian emergency department anaphylaxis cohort. J Allergy Clin Immunol

Pract. 2019;7(7):2232–8.e3.

Brown SG, Stone SF, Fatovich DM, et al. Anaphylaxis: clinical patterns, mediator release, and

severity. J Allergy Clin Immunol. 2013;132(5):1141–9.e5.

Worm M, Francuzik W, Renaudin J-M, Bilo MB, Cardona V, Hofmeier KS, et al. Factors

increasing the risk for a severe reaction in anaphylaxis: an analysis of data from the European

anaphylaxis registry. Allergy. 2018;

Hochstadter E, Clarke A, De Schryver S, LaVieille S, Alizadehfar R, Joseph L, et al. Increasing

visits for anaphylaxis and the benefits of early epinephrine administration: a 4-year study at

a pediatric emergency department in Montreal, Canada. J Allergy Clin Immunol [Internet].

2016 [

Ellis AK. Priority role of epinephrine in anaphylaxis further underscored--the impact on biphasic anaphylaxis. Ann Allergy Asthma Immunol [Internet]. 2015

Who is at risk for biphasic anaphylaxis?

- Severity of symptoms at onset higher (including with hypotension) - generally accepted, braodly supported in studies (Brown et al)

But there is NO validated anaphylaxis severity score

- Consider things that increase risk of severe reactions, but not necessarily proven to increase risk of BA : male sex, age, drug, and venom culprit allergens

- Delayed administration of epinephrine!

Pre-hospital epi decreases risk of needing multiple ED doses of epi

Recieving epi within 60 min of symptom onset decreases risk of BA

People observed with BA were found to have delayed administration (Hochstader, 2016) (Ellis, 2015)

Anaphylaxis - why wait?

Sara Rohrbaugh

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