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

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

Podcast Link: SGEM57
Date:  December 13, 2013

2061c0b2eae6f437683226ea02eb9cf2Guest Skeptic: Dr. Anand Swaminathan or Swami. He is an assistant program director at NYU/Bellevue Hospital in the department of EM. Swani’s interests are in resident education, critical care and EBM. Swami loves debunking urban legends in EM and is a strong supporter of FOAMed.

Case Scenario: 25yo medical student who is allergic to peanuts accidentally eats a cookie at the school holiday party. He arrives to the emergency department covered in hives, hypotensive, short of breath and vomiting. The resident diagnoses him with anaphylaxis and does a great job in treating the reaction. The patient is stable and you are considering discharging him home. However, what about that thing called a biphasic anaphylactic response?

Question: How long should you observe someone after anaphylaxis?

Background: Definition of anaphylaxis.  Simons FER et al. 2012 update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol 2012, 12:389–399

Screen Shot 2013-12-17 at 11.02.21 PM

Treatment for Anaphylaxis:

1. Epinephrine – 1st line treatment. Give it early, give the right dose and give it the right way (IM).

  • Nonspecific alpha and beta agonist
  • Should be given to all patients with anaphylaxis
  • Optimal: 0.3 – 0.5 mg of 1:1000 epinephrine IM (IM in thigh shown to better than SQ in shoulder)
  • Dangers – only seen when wrong dose or wrong route
  • I’ve given inhaled epinephrine for airway swelling. Not much literature. I usually do it with lidocaine or other topical anesthetic in preparation for intubation
  • All other treatments are secondary as effects are delayed at best

2. Inhaled Beta Agonist – May be useful in wheezing or other lower airway issues
3. H1 Blocker (diphenhydramine) – may be useful but has delayed action.
4. H2 blocker (ranitidine) – may be useful because about 10% of histamine receptors on skin are H2
5. Steroids – 4-6 hours before any help

Biphasic Anaphylactic Reactions: We are all taught to fear this reaction. A patient comes in with anaphylaxis or an allergic reaction. We treat them, they get better and then we decide on an observation period. After this they go home. Some percentage of patients will have a biphasic response. They’ll go home and have recurrent anaphylaxis.

Prior studies have shown biphasic reaction rates ranging from 3 – 20% (Tole et al 2007). As a result, some authors have recommended observation for up to 24 hours after an anaphylactic reaction. The truth is that there are no consistent recommendations about observation. Tole et al concluded:

  • “although extended observation would be justified in patients with severe or protracted anaphylaxis, the added costs and resource use involved in routine prolonged monitoring of patients whose symptoms have resolved may worsen ED crowding while likely adding little to individual patient safety.”

Even if we believe the rate of biphasic reactions can be up to 20%, what we want to know is when and how bad. So we want to look at clinically significant biphasic reactions. As far as when, the literature shows that the biphasic reaction can be delayed. It can occur anywhere from 5 minutes up to 3-4 days out. So watching them for 24 hours may not make sense. There’s not much on how bad these reactions can be. Worst-case scenario is that they die from the recurrent reaction.

Reference: Grunau BE et al. Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients with Allergic Reactions or Anaphylaxis. Ann of EM 2013.

Authors 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.”

  • Population: Adult presenting to two urban EDs (age > 17yo) with allergic reactions
  • Intervention: Retrospective chart review
  • Control: NA
  • Outcome: Primary (biphasic reaction) and secondary (mortality)
  • Excluded: < 17 yo, primary diagnosis was asthma w/ allergy as secondary, patient left ED prior to treatment or patient had preexisting condition of angioedema.


  • 428,634 ED visits over 5 years
  • 2,819 (0.66%) were reviewed
  • 496 (18%) classified anaphylactic
  • 2,323 (82%) considered allergic
  • 185 patients had at least 1 subsequent visit for allergic symptoms (bounce-back)
  • 5 (0.18%) clinically important biphasic reactions were identified (95% CI 0.07% to 0.44%)
  • 2 biphasic reactions occurred during the ED visit and 3 (0.1%) 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%)
  • No fatalities (95% CI 0% to 0.17%)

EBM Comments: This was a retrospective chart review of consecutive adult patients presenting to the ED with allergic reaction or anaphylaxis. The methods were very good and specifically cite following the Gilbert et al 1996 and Worster et al 2004 criteria.


Method Criterion



Abstractors Training Three abstractor were trained on 50 charts


Case Selection Criteria “Allergic Reaction” was the sole code available to physicians in their EMR


Variable Definition Very clear definitions were used


Abstraction Forms Standardized MS-Excel spread sheet


Performance Monitoring Weekly meetings


Blind to Hypothesis No, but all variables were entered before evaluation of the outcomes.


IRR Mentioned Yes


IRR Tested Yes, 5% of the cases were randomly selected and reviewed by second individual blinded to patient outcomes


Medical Record Identified Yes, EMR


Sampling Method Yes


Missing Data They describe how they dealt with missing data


Ethics Yes


Hess DR. Retrospective Studies and Chart Reviews. Respiratory Care 2004.

Hess DR. Retrospective Studies and Chart Reviews. Respiratory Care 2004.

  1. Retrospective – 104 diagnosed allergic patients had missing data (not all 3 vital signs of BP/O2 Sat and RR). There are also the usual strengths and weaknesses to this type of study.
  2. Blinding – Abstractors were not blinded to outcome but variables were entered before evaluation of the outcomes
  3. Protocol – No defined protocol for managing allergic reactions
  4. Missing Patients – Some patients may have been missed (presented to primary care physician’s office, 20 patients had no health card, or a patient may have left the province and received care)
  5. Coding – Patients could have been miscoded  (shock undefined, rash, etc)

Does this change what you do? No.

If rash only:

1) H1 Blocker (Diphenhydramine) – 25-50mgPO/IM/IV q2-4hr prn max 300mg/d

  • Cochrane SR Conclusion: “The very limited evidence provided by this review was based on a few old studies of a relatively small size, which we categorised as having high to unclear risk of bias. Thus, at present, the review does not allow confident decision-making about the use of H1-receptor antagonists for urticaria. Although some of these studies have reported a measure of relief of symptoms of urticaria and rather minimal clinical improvement in some of the participants, the evidence was weak and unreliable. We have emphasised the lack of precision and limitations in the reported data where appropriate in this review.”

2) H2 Blocker (Ranitidine) – 50mg IV or 150mg PO

  • Cochrane SR Conclusion:“Based on this review, we are unable to make any recommendations for clinical practice. Randomized controlled trials are needed, although these are likely to prove challenging to design and execute.”

3) Prednisone – (maybe give in rash only) 1mg/kg up to max of 50mg PO daily for 5 days.

  • Cochrane SR Conclusion: “We are, based on this review, unable to make any recommendations for the use of glucocorticoids in the treatment of anaphylaxis.” 


The above treatments plus epinephrine 0.3 – 0.5 mg of 1:1000 IM

  • Epinephrine Cochrane SR Conclusion:  “Based on this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. Although there is a need for randomized, double-blind, placebo-controlled clinical trials of high methodological quality in order to define the true extent of benefits from the administration of adrenaline in anaphylaxis, such trials are unlikely to be performed in individuals with anaphylaxis. Indeed, they might be unethical because prompt treatment with adrenaline is deemed to be critically important for survival in anaphylaxis. Also, such studies would be difficult to conduct because anaphylactic episodes usually occur without warning, often in a non-medical setting, and differ in severity both among individuals and from one episode to another in the same individual. Consequently, obtaining baseline measurements and frequent timed measurements might be difficult, or impossible, to obtain. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular (i.m.) injection should still be regarded as first-line treatment for the management of anaphylaxis.”
  • Watch for a couple of hours (2-3)
  • If no recurrent reaction, go home in 2-3 hours w/ epi pen and steroids
  •  If require repeat epi, get admitted.

should_i_stay_or_should_i_go_t_shirt-rdec5742ddc204ceebbc861060e4f43b6_i80w6_512Bottom Line: Prolonged observation is likely unnecessary in patients who’s symptoms resolve with therapy in the ED. Biphasic reactions are rare and can occur anywhere from 10 minutes up to 6 days.

Case Resolution: Medical student is treated with epinephrine, H1 and H2 blockers. Is observed for 3 hours. Reassessed and doing well with no vomiting, hives resolving and no shortness of breath. He is discharged home with epinephrine auto injector and oral steroids and told avoid his triggers,

Keener Kontest: Last weeks winner from the BEEM Me Up episode was Daniel Mackay. He knew that Dr. Chris Carpenters H-factor was 16. The question this week is name top three categories which trigger anaphylaxis? If you know the answer, send an email to with keener in the subject line. The first person will receive a cool skeptical stocking stuffer prize.

This will be the last episode of the SGEM for 2013. I have one more special edition episode to complete. It will have a holiday surprise to say thanks to all the SGEM listeners.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.