Food-induced anaphylaxis and repeated epinephrine treatments

doi:10.1016/S1081-1206(10)60568-6

Annals of Allergy, Asthma & Immunology

Volume 99, Issue 5, November 2007, Pages 429-432

https://doi.org/10.1016/S1081-1206(10)60568-6 Get rights and content

Background

Research on the use of more than 1 dose of epinephrine in the treatment of food-induced anaphylaxis is limited.

Objective

To perform a medical record review to examine the frequency of repeated epinephrine treatments in patients presenting with food-induced anaphylaxis to the emergency department (ED).

Methods

We reviewed 39 medical records of patients who presented with food-induced allergic reactions to the Massachusetts General Hospital ED during a 1-year period. The analysis focused on the timing of the onset of symptoms and on the number of epinephrine treatments given before and during the ED visit.

Results

Of the 39 patients, 34 had an acute food-induced allergic reaction. Nineteen had anaphylaxis. Twelve patients with anaphylaxis (63%; 95% confidence interval, 38%-84%) received at least 1 dose of epinephrine, and 3 (16%; 95% confidence interval, 3%-40%) were given 2 doses. Although statistical analysis was not possible, repeated epinephrine treatment occurred in patients with anaphylaxis to peanut or tree nut and hypotension. There was no apparent association between time from ingestion of the causative agent to epinephrine treatment(s).

Conclusions

Of patients presenting to the ED with food-induced anaphylaxis, approximately 16% were treated with 2 doses of epinephrine. This study supports the recommendation that patients at risk for food-induced anaphylaxis carry 2 doses of epinephrine. Further study is needed to confirm these results and to expand them to patients who do not present to the ED because that group may have a lower frequency of epinephrine use.

Section snippets

INTRODUCTION

Food-induced anaphylaxis is a life-threatening acute allergic reaction that leads to at least 29,000 emergency department (ED) visits in the United States each year.¹ In addition, approximately 125 to 150 deaths per year are attributed to food-induced anaphylaxis.¹ Prompt recognition and treatment of these reactions are critical to preventing substantial morbidity and mortality.

In 2005 the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and

METHODS

This study was performed as an extension of an earlier study by Clark et al⁷ in 2004 that evaluated the management of food-induced allergic reactions in the ED. We obtained identifying information from this previously identified case series (found using International Classification of Diseases, Ninth Revision, codes 693.1, 995.0, 995.3, and 995.60-995.69) and, under the same institutional review board approval, reviewed the medical records of patients who presented to the Massachusetts General

RESULTS

Of 40 patients presenting to the Massachusetts General Hospital ED for food-induced reactions between June 1, 1999, and June 30, 2000, 39 medical records were available for review. Thirty-four patients were deemed to have had an acute allergic reaction due to food ingestion. Of these patients, 19 (56%) were considered to have met the criteria for anaphylaxis as defined by the 2005 symposium on the definition and management of anaphylaxis.³ Fourteen of the 34 patients (41%) with a food-induced

DISCUSSION

To our knowledge, this is the first study to document multiple epinephrine treatments administered in the management of anaphylaxis in the ED setting. We found that of 19 patients with food-induced anaphylaxis presenting to the ED of the Massachusetts General Hospital, 3 (16%) received 2 doses of epinephrine. Although statistical analysis was not possible, repeated epinephrine treatment occurred in patients with anaphylaxis to peanut or tree nut and hypotension. There was no apparent

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Cited by (65)

Emergency medicine updates: Anaphylaxis
2021, American Journal of Emergency Medicine
Anaphylaxis is a potentially deadly condition that requires emergent therapy. While frequently treated in the emergency department (ED), recent evidence updates may improve the diagnosis and management of this condition.
This paper evaluates key evidence-based updates concerning the diagnosis and management of anaphylaxis for the emergency clinician.
The presentation of anaphylaxis can vary. Current diagnostic criteria can be helpful when evaluating patients for anaphylaxis, though multiple criteria exist. While the most common causes of anaphylaxis include medications, insect venom, and foods, recent literature has identified an IgE antibody response to mammalian galactose alpha-1,3-galactose, known as alpha-gal anaphylaxis. Epinephrine is the first-line therapy and is given in doses of 0.01 mg/kg (up to 0.5 mg in adults) intramuscularly (IM) in the anterolateral thigh. Intravenous (IV) epinephrine administration is recommended in patients refractory to IM epinephrine and IV fluids, or those with cardiovascular collapse. Antihistamines and glucocorticoids should not delay administration of epinephrine and do not demonstrate a significant reduction in risk of biphasic reactions. Biphasic reactions may affect 1–7% of patients with anaphylaxis. Risk factors for biphasic reaction include severe initial presentation and repeated doses of epinephrine. Disposition of patients with anaphylaxis requires consideration of several factors.
Emergency clinicians must be aware of current updates in the evaluation and management of this disease.
Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis
2021, Journal of Allergy and Clinical Immunology
Regulatory bodies recommend that all patients at risk of anaphylaxis be prescribed 2 epinephrine autoinjectors, which they should carry at all times. This is in contrast to some guidelines. The proportion of anaphylaxis reactions that are treated with multiple doses of epinephrine has not been systematically evaluated.
Our aim was to undertake a systematic review and meta-analysis of published studies reporting epinephrine treatment for anaphylaxis in which data relating to the number of doses administered were available.
We searched the Medline, Embase, and Cochrane databases for relevant studies reporting at least 10 anaphylaxis events (due to food or venom) from 1946 until January 2020. Data were extracted in duplicate for the meta-analysis, and the risk of bias was assessed. The study was registered under the PROSPERO identifier CRD42017069109.
A total of 86 studies (36,557 anaphylaxis events) met the inclusion criteria (20 of the studies [23%] were prospective studies; 64 [74%] reported reactions in the community, and 22 [26%] included food challenge data). Risk of bias was assessed as low in 50 studies. Overall, 7.7% of anaphylaxis events from any cause (95% CI = 6.4-9.1) were treated with multiple doses of epinephrine. When only epinephrine-treated reactions for which subsequent doses were administered by a health care professional were considered, 11.1% of food-induced reactions (95% CI = 9.4-13.2) and 17.1% of venom-induced reactions (95% CI = 11.3-25.0) were treated with more than 1 epinephrine dose. Heterogeneity was moderate to high in the meta-analyses, but at sensitivity analysis this estimate was not affected by study design or anaphylaxis definition.
Around 1 in 10 anaphylaxis reactions are treated with more than 1 dose of epinephrine.
European Resuscitation Council Guidelines 2021: First aid
2021, Resuscitation
The European Resuscitation Council has produced these first aid guidelines, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics include the first aid management of emergency medicine and trauma. For medical emergencies the following content is covered: recovery position, optimal positioning for shock, bronchodilator administration for asthma, recognition of stroke, early aspirin for chest pain, second dose of adrenaline for anaphylaxis, management of hypoglycaemia, oral rehydration solutions for treating exertion-related dehydration, management of heat stroke by cooling, supplemental oxygen in acute stroke, and presyncope. For trauma related emergencies the following topics are covered: control of life-threatening bleeding, management of open chest wounds, cervical spine motion restriction and stabilisation, recognition of concussion, cooling of thermal burns, dental avulsion, compression wrap for closed extremity joint injuries, straightening an angulated fracture, and eye injury from chemical exposure.
Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying Hymenoptera?
2019, Annals of Allergy, Asthma and Immunology
Hymenoptera venom allergy (HVA) is a well-established cause of anaphylaxis; however, studies comparing patients with imported fire ant (IFA) to flying hymenoptera (FH) allergies are lacking.
This study sought to characterize the initial presentation and examine differences between patients with IFA and FH reactions.
A multiyear (2007-2014), observational, single-institution analysis of patients referred for evaluation of HVA was performed. Data was obtained via physician interview, chart review and specific IgE results.
175 patients were enrolled with no difference between FH and IFA patients when analyzing mean age, sex or likelihood to seek emergency department (ED) care. Asthma was similar in all groups at 21%. ED treatments were also similar (epinephrine: 32/150, 21%; antihistamines: 141/155, 91%; corticosteroids: 67/148, 45%). Reaction severity correlated with likelihood of ED visit (P <.001), use of epinephrine (P <.001) and corticosteroid use (P <.05). Patients presenting to the ED with anaphylaxis received epinephrine in 27/73 (37%) of cases. Overall, 149/175 (85%) patients in our cohort were confirmed to be sensitized to hymenoptera. Of those with positive testing 127/149 (85%) chose to pursue VIT.
IFA and FH patients have many similarities at presentation. Asthma occurred 2.5 times more frequently our cohort compared to the general US population. Epinephrine administration in our cohort was suboptimal. Children have initial reactions and are treated in the ED similarly to adults, with a notable (although not statistically significant) reduced use of epinephrine. The majority of patients seen in the ED and subsequently followed up in an allergy clinic had their venom allergy confirmed and initiated life-saving immunotherapy.
An economic evaluation of immediate vs non-immediate activation of emergency medical services after epinephrine use for peanut-induced anaphylaxis
2019, Annals of Allergy, Asthma and Immunology
Layperson food allergy management plans commonly stipulate that if epinephrine is used to immediately call 911 and seek care in the nearest medical facility for observation.
To evaluate the cost-effectiveness of this strategy, vs a watchful waiting approach before activating emergency medical services (EMS).
We performed a cost-effectiveness analysis using Markov modeling simulated over a 20-year horizon comparing activating EMS immediately after epinephrine use for allergic reactions to peanut vs a “wait and see” approach in which EMS was only activated if symptoms of the reaction did not promptly resolve after treatment. The base-case model assumed a 10-fold increased fatality risk with delayed EMS activation.
The fatality risk associated with early EMS use was minimal, with a per-patient fatality rate over a 20-year horizon of 1.2 × 10⁻⁶, vs 1.9 × 10⁻⁶ for a wait and see approach. The incremental cost per life-year saved was $142,943,447 for early EMS vs wait and see, with the cost per death prevented reaching $1,349,335,651 as the simulation concluded. Cost of early EMS activation rose to $321,625,534 per life-year saved ($3,035,454,848 per death prevented) if a 5-fold increase in fatality risk was assumed, and was $12,997,173 per life-year saved ($122,689,936 per death prevented) if a 100-fold increase in fatality risk was assumed.
Medical observation of a treated and promptly resolved peanut allergic reaction has minimal benefit and excessive costs. Immediately activating EMS after using epinephrine for a peanut allergic reaction in this context is not cost-effective.
Risk factors for multiple epinephrine doses in food-triggered anaphylaxis in children
2018, Annals of Allergy, Asthma and Immunology
Food-related anaphylactic reactions may require treatment with more than 1 dose of epinephrine. Current guidelines advise patients at risk of anaphylaxis to carry 2 epinephrine autoinjectors.
The objective of this study was to determine risk factors of multiple-dose epinephrine treatment in pediatric food-related anaphylaxis.
Parents of children with physician-confirmed diagnosis of food allergy were administered a standardized questionnaire at the time of their clinic visit. These patients were then followed-up prospectively by phone.
Six hundred forty-two subjects had allergic reactions. Twenty-six percent of patients reported at least 1 reaction treated with epinephrine, for a total of 221 reactions. Among reactions treated with epinephrine, 24 reactions (11%) received 2 or more doses of epinephrine. The most common triggers were milk (30%) and peanut (18%). Milk-triggered allergic reactions (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.2–8.4) and treatment with oxygen (OR 5.0, 95% CI 2.0–12.4) were significant risk factors for requiring multiple doses of epinephrine to treat an allergic reaction.
This study demonstrates that treatment of anaphylaxis may require more than 1 epinephrine injection. Reactions triggered by milk or requiring treatment with oxygen are at higher risk for needing more than 1 dose of epinephrine. Families of food-allergic children should be counseled on the importance of carrying 2 epinephrine auto-injectors.

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: Dr Camargo has received funding for consulting and investigator-initiated research from Dey Laboratories and Verus Pharmaceuticals.

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Original Articles: Systemic Allergic DisordersFood-induced anaphylaxis and repeated epinephrine treatments

Background

Objective

Methods

Results

Conclusions

Section snippets

INTRODUCTION

METHODS

RESULTS

DISCUSSION

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Original Articles: Systemic Allergic Disorders
Food-induced anaphylaxis and repeated epinephrine treatments