Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis

Patel, Nandinee; Chong, Kok Wee; Ierodiakonou, Despo; Bartra, Joan; Boyle, Robert; Turner, Paul J.

doi:10.1016/j.jaci.2021.03.042

Cited by 53 publications

(43 citation statements)

References 90 publications

(125 reference statements)

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“…Around 10% of anaphylaxis events demonstrate a suboptimal response to a single dose of adrenaline; most will respond to one or two further doses. 32 Overall, the evidence for adrenaline to treat anaphylaxis was graded as moderate certainty (Table 2) À while confidence in the effect estimate is limited, data from a systematic review and metaanalysis (including 36,557 anaphylaxis events) indicates that only 2.2% (95% CI 1.1À4.1%) of reactions fail to respond to two doses of adrenaline. 32 It was deemed very unlikely that the true effect would be substantially different from this estimate, thus under the EtD framework (Table 2) the certainty was assigned as moderate.…”

Section: For Policy Makersmentioning

confidence: 99%

“…32 Overall, the evidence for adrenaline to treat anaphylaxis was graded as moderate certainty (Table 2) À while confidence in the effect estimate is limited, data from a systematic review and metaanalysis (including 36,557 anaphylaxis events) indicates that only 2.2% (95% CI 1.1À4.1%) of reactions fail to respond to two doses of adrenaline. 32 It was deemed very unlikely that the true effect would be substantially different from this estimate, thus under the EtD framework (Table 2) the certainty was assigned as moderate. The strong recommendation for adrenaline is based on the working group placing a high value on evidence suggesting that adrenaline is the most appropriate treatment to reduce morbidity, recommendations for its use in existing anaphylaxis guidelines, and feedback from the public consultation.…”

Section: For Policy Makersmentioning

confidence: 99%

“…Around 10% of anaphylaxis reactions (predominantly community reactions to food allergens) have a suboptimal response to a single dose of IM adrenaline, but 98% will respond to 1 or 2 further doses. 32 While effective for respiratory symptoms, a single dose of IM adrenaline has a limited effect on reversing the decrease in stroke volume seen during peanut-induced anaphylaxis. 51 Case series of refractory anaphylaxis 30,52 and evidence from animal models 31,53 indicate that a poor response to adrenaline is likely due to insufficient adrenaline delivery (a combination of both inadequate dosing with adrenaline, and insufficient circulatory capacity to ensure adequate dose-distribution).…”

Section: Rationalementioning

confidence: 99%

“…30,54 At least 98% of reactions reported in the literature respond to a maximum of 3 doses of IM adrenaline. 32 The working group therefore suggests that following a suboptimal response to 2 doses of adrenaline, expert input is urgently sought to establish a low dose IV adrenaline infusion to provide further vasopressor support (on the basis that this will take at least 5 min to set-up, during which a third bolus dose of IM/IV adrenaline should be administered). Given the potential risks of intravenous adrenaline infusion without the necessary expertise and support, and evidence supporting the use of intravenous adrenaline infusions for refractory reactions, we make a strong recommendation that urgent expert support is obtained to establish an intravenous adrenaline infusion to treat refractory anaphylaxis.…”

Section: Rationalementioning

confidence: 99%

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Evidence update for the treatment of anaphylaxis

et al. 2021

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The Resuscitation Council UK has updated its Guideline for healthcare providers on the Emergency treatment of anaphylaxis. As part of this process, an evidence review was undertaken by the Guideline Working Group, using an internationally-accepted approach for adoption, adaptation, and de novo guideline development based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework, referred to as GRADE-ADOLOPMENT. A number of significant changes have been made, which will be reflected in the updated Guideline.These include: emphasis on repeating intramuscular adrenaline doses after 5 min if symptoms of anaphylaxis do not resolve; corticosteroids (e.g. hydrocortisone) no longer being routinely recommended for the emergency treatment of anaphylaxis; interventions for reactions which are refractory to initial treatment with adrenaline; a recommendation against the use of antihistamines for the acute management of anaphylaxis; and guidance relating to the duration of observation following anaphylaxis, and timing of discharge.

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Section: For Policy Makersmentioning

confidence: 99%

Section: For Policy Makersmentioning

confidence: 99%

Section: Rationalementioning

confidence: 99%

Section: Rationalementioning

confidence: 99%

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Evidence update for the treatment of anaphylaxis

et al. 2021

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“…Estimates refer to occurrence of allergic symptoms at ED 05 levels of exposure in food-allergic individuals. 15 , 16 , 17 , 18 , 19 ED 05 , Amount of allergen expected to cause objective symptoms in 5% of the population with that allergy. …”

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confidence: 99%

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis

Turner

Patel

Ballmer‐Weber

et al. 2022

The Journal of Allergy and Clinical Immunology: In Practice

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Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed “reference doses,” below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure.

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Management of Food Allergies and Food-Related Anaphylaxis

Iglesia,

Kwan,

Virkud

et al. 2024

JAMA

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ImportanceAn estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults.ObservationsIn the US, 9 foods account for more than 90% of IgE-mediated food allergies—crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration–approved oral immunotherapy product for treatment of peanut allergy.Conclusions and RelevanceIgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites.

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Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis

Cited by 53 publications

References 90 publications

Evidence update for the treatment of anaphylaxis

Evidence update for the treatment of anaphylaxis

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis

Management of Food Allergies and Food-Related Anaphylaxis

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