Is there evidence to support early epinephrine administration for treatment of hypersensitivity reactions?

Comment by InpharmD Researcher

Limited data in pediatric patients suggests that early epinephrine exposure prior to arrival at the emergency department (ED) is potentially associated with reduced number ED epinephrine doses, lower risk of hospitalization, and increased discharge rates. However, the results were largely derived from retrospective studies which are susceptible to documentation bias and differences in how anaphylactic reactions were treated across study sites.
Background

A 2016 letter to the editor discussed risks and benefits of early epinephrine administration for treatment of anaphylaxis. The letter describes experience from a single pediatric hospital, finding that administration of epinephrine before arrival of the patient to the emergency department (ED) is associated with a decreased likelihood of requiring multiple doses of epinephrine in the ED, reflecting the benefit of more prompt or early administration. This conclusion is derived from a multivariate analysis, which revealed an odds ratio of 0.25 (95% confidence interval 0.04 to 0.6) for use of epinephrine outside of the ED and later need for ≥ 2 doses of epinephrine in the ED. [1]

A 2017 retrospective review article primarily investigated the factors associated with anaphylaxis management prior to arrival at the ED or urgent care, but also included a subanalysis of whether receiving prehospital epinephrine affected outcomes. The population consisted of 408 pediatric patients with a record of anaphylactic reaction to food. A total of 264 patients (64.7%) had known prior history of anaphylactic reaction and 195 (47.9%) had previously been prescribed self-injectable epinephrine. Patients who received epinephrine prior to arrival were found to be significantly less likely to be subsequently treated with epinephrine (odds ratio [OR] 0.07; 95% confidence interval [CI] 0.04 to 0.13). Furthermore, prehospital epinephrine use was associated with lower hospitalization rates compared to those who did not receive epinephrine (OR 0.56; 95% CI 0.37 to 0.86). The majority of patients who were transferred from urgent care to the ED for further treatment or observation did not receive epinephrine prior to arrival (91%). There were no reported deaths in either cohort. These findings suggest that earlier administration of epinephrine prior to hospitalization has greater potential for clinical benefits. However, the primary focus of the study was an assessment of different factors and not to establish a difference in delaying epinephrine. [2]

References:

[1] Hochstadter E, Clarke A, De Schryver S, 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. 2016;137(6):1888-1890.e4. doi:10.1016/j.jaci.2016.02.016
[2] Robinson M, Greenhawt M, Stukus DR. Factors associated with epinephrine administration for anaphylaxis in children before arrival to the emergency department. Ann Allergy Asthma Immunol. 2017;119(2):164-169. doi:10.1016/j.anai.2017.06.001
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there evidence to support early epinephrine administration for treatment of hypersensitivity reactions?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

 

Early Treatment of Food-Induced Anaphylaxis with Epinephrine Is Associated with a Lower Risk of Hospitalization

Design

Retrospective chart review

N= 384

Objective

 To identify factors associated with early epinephrine treatment for FIA and to specifically examine the association between early epinephrine treatment and hospitalization

Study Groups

Early epinephrine (n= 164)

Late epinephrine (n= 70)

Inclusion Criteria

 Age < 18 years old, food-induced acute allergic reaction

Exclusion Criteria

 N/A

Methods

Data was collected from a single pediatric tertiary care center in the United States. A food-induced acute allergic reaction was defined as acute IgE-mediated symptoms lasting <72 hours from ingesting a suspected food trigger within 2 hours. Food-induced anaphylaxis (FIA) was defined as a reaction meeting criteria for anaphylaxis per the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network (NIAID-FAAN) Guidelines and/or requiring epinephrine treatment.

Duration

 Data collection: January 1, 2004 to December 31, 2009

Outcome Measures

 Use of epinephrine after arriving to the emergency department (ED), ED disposition

Baseline Characteristics

  

Early epinephrine (n= 164)

Late epinephrine (n= 70)

  

Age, years

 7.4 4.3  

Female

58% 53%  

White

 80% 65%  

Medial history

Known allergy to offending allergen

Known allergic problems

Asthma

Patient owns epinephrine autoinjector

 

66%

82%

62%

80%

 

34%

69%

44%

23%

  

Reaction cause

Peanuts

Tree nuts

Seeds

Fruits and vegetables

Shellfish

Fish

Milk products

Eggs

Wheat

 

40%

21%

1%

2%

4%

1%

15%

6%

1%

 

33%

29%

0

4%

10%

4%

4%

7%

0

  

Time from exposure to ED triage

< 1 hour

1-3 hours

4-6 hours

> 7 hours

 

37%

54%

6%

4%

 

47%

43%

8%

2%

  

Number of pre-ED epinephrine doses

0

1

2+

 

0

95%

5%

 

70%

0

0

  

Results

Endpoint

Early epinephrine (n= 164)

Late epinephrine (n= 70)

p-Value

Number of ED epinephrine doses

0

1

2+

 

93%

5%

2%

 

0

89%

11%

 <0.001

ED disposition

Discharged home

Admitted to observation unit

Admitted to floor

Admitted to ICU

17%

83%

10%

6%

1%

42%

57%

23%

17%

1%

<0.001

<0.001

--

--

--

After adjusting for age, sex, and race, patients who received early epinephrine treatment had a significantly lower risk of hospitalization compared to those who received late epinephrine treatment (odds ratio 0.25, 95% confidence interval [CI] 0.12-0.49).

Adverse Events

 N/A

Study Author Conclusions

 In this population, early treatment of FIA with epinephrine was associated with significantly lower risk of hospitalization. Accordingly, this study supports the benefit of prompt administration of epinephrine for the treatment of FIA.

InpharmD Researcher Critique

 Case identification relied on ICD-9 codes, which could have resulted in miscoding and exclusion of visits. Documentation by emergency services was often poor, possibly under-representing pre-hospital symptoms. Clinical decision-making regarding hospitalization can vary and include non-clinical factors. Lastly, the study could not determine exact time frames of epinephrine administration due to chart review limitations.



References:

Fleming JT, Clark S, Camargo CA Jr, Rudders SA. Early treatment of food-induced anaphylaxis with epinephrine is associated with a lower risk of hospitalization. J Allergy Clin Immunol Pract. 2015;3(1):57-62. doi:10.1016/j.jaip.2014.07.004