Background: Anaphylaxis is a condition that represents the best of Emergency Medicine: rapid onset of life-threatening symptoms that can be reversed with expeditious interventions. It is defined as the presence of any of the following:

  1. Both skin (or mucosal tissue) involvement along with either respiratory compromise or a SBP < 90 mm Hg or . . .
  2. Two of the following after exposure to a likely allergen
  3. Skin (or mucosal tissue) involvement
  4. Respiratory compromise
  5. SBP < 90 mm Hg
  6. Gastrointestinal symptoms or . . .
  7. SBP < 90 mm Hg after exposure to a known allergen

A biphasic anaphylactic reaction occurs when a patient is treated for their anaphylaxis, symptoms resolve and then after some intervening asymptomatic time period, the anaphylaxis returns. This is the dreaded complication the Emergency Providers fear. Prior publications have quoted biphasic allergic rates from 3-20% (Tole 2007). However, this number includes minor biphasic reactions (i.e. hives) and not just anaphylaxis. The risk of a biphasic reaction has led providers to hold patients in the ED for “observation” for symptom recurrence. Although there is no clear literature on how long to observe patients, 4-6 hours is often quoted and taught.

Clinical Question

How long should a patient who presents with anaphylaxis and has resolution of symptoms with treatment be observed in the ED?


Adult presenting to two urban EDs (age > 17yo) with allergic reactions


Primary Outcome: Biphasic Reactions
Secondary Outcome: Death


Retrospective chart review of consecutive adult patients presenting to the ED with an allergic reaction or anaphylaxis.


< 17 yo, primary diagnosis was asthma w/ allergy as secondary, patient left ED prior to treatment or patient had preexisting condition of angioedema.

Primary Results

  • 428,634 ED visits over 5 years
  • 2,819 (0.66%) charts with a diagnosis of allergic reaction or anaphylaxis were reviewed
  • 496 classified anaphylactic
  • 2,323 considered allergic
  • 185 patients had at least 1 subsequent visit for allergic symptoms

Rate of clinically important biphasic reaction: 0.18% (95% CI 0.07% to 0.44%)

Details of 5 Clinically Important Biphasic Reactions

  • 2 biphasic reactions occurred during the ED visit and 3 post-discharge
  • 2 (0.4%) biphasic reactions were in the anaphylaxis group (95% CI 0.07 to 1.6%)
  • 3 (0.13%) biphasic reactions occurred in the allergic reaction group (95% CI 0.03% to 0.41%)

There were no fatalities (95% CI 0% to 0.17%)


  • Methods in this chart review were excellent. The specifically site following the Gilbert 1996 and Worster 2004
  • Large database with high likelihood that patient’s representations were captured.


  • Retrospective Study – 104 charts with incomplete data
  • No blinding
  • No defined protocol for managing allergic reactions
  • Patients may have been missed (presented to PCP, 20 pts had no health card, or left the province)
  • Coding issues (could have been miscoded – shock, rash, etc)

Author's Conclusions

“Among ED patients with allergic reactions or anaphylaxis, clinically important biphasic reactions and fatalities are rare. Our data suggest that prolonged routine monitoring of patients whose symptoms have resolved is likely unnecessary for patient safety.”

Our Conclusions

We agree with the authors’ conclusions.

Potential Impact To Current Practice

This study sheds light on the utility of prolonged ED observation in patients with anaphylaxis and symptom resolution and has the potential to shorten traditional observation periods.

Bottom Line

Prolonged observation is likely unnecessary in patients whose symptoms resolve with therapy in the ED. Biphasic reactions are rare and can occur anywhere from 10 minutes up to 6 days.

Read More

SGEM#57: Should I Stay Or Should I Go (Biphasic Anaphylactic Response)

REBEL Cast Episode 1: Clinically Important Biphasic Anaphylaxis

Additional References

Tole JW, Lieberman P. Biphasic Anaphylaxis: Review of Incidence, Clinical Predictors and Observation Recommendations. Immunol Allergy Clin N Am 2007; 27: 309-26. PMID: 17493505