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Cover of Epinephrine Auto-Injectors for Anaphylaxis: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines

Epinephrine Auto-Injectors for Anaphylaxis: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines

CADTH Rapid Response Report: Summary with Critical Appraisal

and .

Abbreviations

AGREE

Appraisal of Guidelines for Research and Evaluation

AMSTAR

A Measurement Tool to Assess systematic Reviews

ANZAAG

Australian and New Zealand Anaesthetic Allergy Group

ANZCA

Australian and New Zealand College of Anaesthetists

CENTRAL

Cochrane Central Register of Controlled Trials

CRD

Centre for Reviews and Dissemination

EAI

Epinephrine auto injector

IM

Intramuscular

IV

Intravenous

JTFPP

Joint Task Force on Practice Parameters

MeSH

Medical Subject Headings

NHMRC

National Health and Medical Research Council

PRISMA

Preferred Reporting Items for Systematics and Meta-Analyses

RCT

Randomized controlled trials

Context and Policy Issues

Anaphylaxis is a potentially life-threatening medical emergency which requires prompt recognition and treatment.1 The condition is caused by a severe and generalized allergic reaction or hypersensitivity reaction that leads to a sudden release of mast cell and basophil-derived mediators into circulation.2,3 Onset of a range of clinical symptoms occurs rapidly, and includes severe airway, breathing, and circulation problems.4 Common causes of anaphylaxis are medication reactions, insect stings, and food allergies.5

Epinephrine is the usual treatment for patients experiencing anaphylactic reactions,2 and the administration of this treatment should be rapidly executed.6 Epinephrine has several mechanisms of action that reduce and reverse the symptoms of anaphylaxis.2,7 It works to decrease vasoconstriction and peripheral vascular resistance, decrease upper airway mucosal edema, increase bronchodilation, and decrease mediator release from mast cells and basophils. Delayed administration of epinephrine is associated with poorer outcomes for the patient, emphasizing the importance of prompt treatment.2 First-line emergency treatment with epinephrine is generally by intramuscular (IM) injection,5 which can either be administered by an epinephrine auto-injector (EAI) or by manual draw-up and dosing from an epinephrine containing ampoule or vial. Depending on the setting, epinephrine can be administered by the patients experiencing the reaction, by a caretaker, or by various health care professionals.8,9 There is uncertainty as to which method of IM delivery of epinephrine is preferable in health care settings, and whether EAI or epinephrine vials for manual delivery should be stocked and available for use by health care professionals.

In order to inform policy decisions about the use of either EAI or manual delivery of epinephrine, specific evidence is required. As such, this report aims to review the comparative clinical effectiveness and cost-effectiveness of EAI versus manually administered epinephrine for the management of individuals with anaphylaxis. Additionally, the report aims to review the evidence-based guidelines for the management of anaphylaxis.

Research Questions

  1. What is the comparative clinical effectiveness of epinephrine auto-injectors versus manually administered epinephrine for the management of individuals with anaphylaxis?
  2. What is the comparative cost-effectiveness of epinephrine auto-injectors versus manually injected epinephrine for the management of individuals with anaphylaxis?
  3. What are the evidence-based guidelines regarding management of anaphylaxis?

Key Findings

No evidence regarding the clinical effectiveness of epinephrine auto-injectors compared to manually administered epinephrine for the management of individuals with anaphylaxis was identified.

No evidence regarding the cost-effectiveness of epinephrine auto-injectors compared to manually administered epinephrine for the management of individuals with anaphylaxis was identified.

Two evidence-based guidelines were identified regarding the management of anaphylaxis. One guideline was jointly developed by the Australian and New Zealand College of Anaesthetists and the Australian and New Zealand Anaesthetic Allergy Group. The other guideline was a practice parameter update by the Joint Task Force on Practice Parameters, which represents the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. Both guidelines recommend epinephrine administration for anaphylaxis, however neither explicitly state a preference for epinephrine auto-injectors versus manually drawn-up epinephrine for the management of individuals with anaphylaxis.

Methods

Literature Search Methods

A limited literature search was conducted by an information specialist on key resources including PubMed, the Cochrane Library, the University of York Centre for Reviews and Dissemination (CRD) databases, the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were epinephrine and anaphylaxis. Filters were applied to limit the retrieval to health technology assessments, systematic reviews and meta-analyses, randomized controlled trials (RCTs), economic studies, non-randomized studies, and guidelines. The search was also limited to English language documents published between January 1, 2015 and March 24, 2020.

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Table 1. Selection criteria.

Table 1

Selection criteria.

Exclusion Criteria

Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to 2015. Guidelines with unclear methodology were also excluded.

Critical Appraisal of Individual Studies

The included publications were critically appraised by one reviewer using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument 10 as a guide. Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included study were described narratively.

Summary of Evidence

Quantity of Research Available

A total of 392 citations were identified in the literature search. Following screening of titles and abstracts, 363 citations were excluded and 29 potentially relevant reports from the electronic search were retrieved for full-text review. Sixteen potentially relevant publications were retrieved from the grey literature search for full-text review. Of these potentially relevant articles, 43 publications were excluded for various reasons, and two publications met the inclusion criteria and were included in this report. These were two evidence-based guidelines. Appendix 1 presents the PRISMA11 flowchart of the study selection. Additional references of potential interest are provided in Appendix 5.

Summary of Study Characteristics

Two evidence-based guidelines1,12 were identified for inclusion in this review. No relevant health technology assessments, systematic reviews, RCTs, non-randomized studies, or economic evaluations were identified. Additional details regarding the characteristics of included publications are provided in Appendix 2, Table 2.

Study Design

Two evidence-based guidelines were included in this report. One guideline1 was jointly developed by the Australian and New Zealand College of Anaesthetists (ANZCA) and Australian and New Zealand Anaesthetic Allergy Group (ANZAAG). The guidelines were published in 2016 as a revision to guidelines originally developed in 2013 by ANZAAG. A systematic literature search was performed, however no relevant RCTs were identified, and therefore the guidelines are consensus statements. The level of evidence and the grades of the recommendation were assessed using a modified version of the National Health and Medical Research Council (NHMRC) levels of evidence (from “Level I” [highest] to “Level V” [lowest]) and the NHMRC grades of recommendation (from “A” [highest] to “D” [lowest]). These assessments of the level of evidence and grade of recommendation were taken from published reviews and other guidelines for the management of anaphylaxis (they were not assessed directly by the ANZCA/ANZAAG guideline authors).

The other guideline12 was developed by the Joint Task Force on Practice Parameters (JTFPP), which represents the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. These practice parameters were a 2015 update from the previously published 2010 parameters. The practice parameters update was formulated using a systematic literature review, in combination with consensus expert opinion and supplementary documents identified by the workgroup. The strength of the recommendations (”Strong Recommendation” to “No Recommendation”) and the quality of evidence (from “A” [highest] to “D” [weakest]) were assessed using unreferenced classification guides.

Country of Origin

The guidelines were developed in the United States12 and Australia and New Zealand.1

Patient Population

The intended users of the ANZCA/ANZAAG guidelines1 were anaesthetists, and the target populations were patients experiencing perioperative anaphylaxis. The intended users of the JTFPP guidelines12 were practicing physicians. The target populations of guidelines were not explicitly stated, but they appear to be intended for patients experiencing anaphylaxis.

Interventions and Comparators

One guideline examined the management (including diagnosis, immediate emergency treatment, and post-emergency treatments) of perioperative anaphylaxis.1 The other guideline provided evidence-based recommendations for the diagnosis and management of anaphylaxis in various settings (e.g., in-office), when exposed to various allergens (e.g., foods or insect stings), and with various medical histories (e.g., patients with mastocytosis).12

Outcomes

The ANZCA/ANZAAG guidelines1 were based on a literature review which identified guidelines for management of anesthetic anaphylaxis as well as on general guidelines for the management of anaphylaxis. The guideline documents included limited details surrounding the inclusion criteria for the literature review; the specific outcomes considered by the guideline development group were not explicitly reported. As no RCTs were identified in the literature search, the ANZCA/ANZAAG guidelines were developed as consensus statements with the objective of optimizing the management of perioperative anaphylaxis for anesthetists. Relevant to this review, the guidelines provided recommendations for: 1) immediate crisis in adults, 2) immediate crisis in pediatrics, 3) refractory management in adults, and 4) refractory management in pediatrics. Recommendations for differential diagnosis and post-crisis management were also included, however they were not relevant to this report.

The JTFPP guidelines12 were based on a systematic literature review which aimed to identify new references to update practice parameters previously published in 2010. The guidelines aimed to improve the care of patients by providing evidence-based recommendations for physicians for the diagnosis and management of anaphylaxis. As with the other guideline in this report, the JTFPP guideline documents included limited details surrounding the inclusion criteria (including the outcomes considered) for the literature review. The guidelines presented recommendations for the general evaluation and management of anaphylaxis for: 1) evaluation and management of patients with a history of anaphylaxis, 2) office management of anaphylaxis, 3) anaphylaxis to foods, 4) anaphylaxis to drugs and biological agents, 5) insect sting anaphylaxis, 6) perioperative anaphylaxis: anaphylaxis before, during, or immediately after anesthesia, 7) seminal fluid anaphylaxis, 8) exercise-induced anaphylaxis, 9) anaphylaxis to subcutaneous allergen immunotherapy extract (vaccine), 10) anaphylaxis in mastocytosis, monoclonal mast cell activating syndrome, and mast cell activating syndrome, and 11) unusual presentations of anaphylaxis.

Summary of Critical Appraisal

Additional details regarding the strengths and limitations of included publications are provided in Appendix 3, Table 3

Guidelines

In both guidelines,1,12 the objectives and health questions were clearly described, the development groups included individuals from all relevant professional groups, and the target users were clearly defined. Additionally, systematic methods were used to identify evidence, strengths and limitations of the evidence were listed, and clear links between the evidence and the recommendations were provided. Overall, the JTFPP guidelines12 provided clear presentation of recommendations. In one guideline,1 the intended population to whom the guideline applies was clearly defined, but not in the other guideline.1 One of the guidelines1 provided tools, in the form of a “toolbox of cards” for putting the recommendations into practice.

Limitations to the guidelines were identified. Neither of the guidelines1,12 stated whether the views and preferences of the target populations were sought. There was a lack of clarity in both guidelines surrounding the methods for formulating the recommendations (including the literature search), the external review process, and the criteria for selecting evidence. The AANZCA/ANZAAG guidelines1 did not clearly provide their recommendations. Furthermore, neither of the guidelines1,12 provided a description of the barriers and facilitators to following the guidelines or the resource implications of the guidelines. The potential influence of the funding bodies and the competing interests were not described in one of the guidelines, and therefore the potential for bias cannot be ruled out.

Summary of Findings

A table of the main study findings and authors’ conclusions are presented in Appendix 4, Table 4.

Clinical Effectiveness of Epinephrine Auto-injectors versus Manually Administered Epinephrine

No relevant evidence regarding the clinical effectiveness of EAI versus manually administered epinephrine for the management of individuals with anaphylaxis was identified; therefore, no summary can be provided.

Cost-Effectiveness of Epinephrine Auto-injectors versus Manually Administered Epinephrine

No relevant evidence regarding the cost-effectiveness of EAI versus manually administered epinephrine for the management of individuals with anaphylaxis was identified; therefore, no summary can be provided.

Guidelines

Relevant to this report, the ANZCA/ANZAAG guidelines1 did not make any explicit distinction or recommendation for EAI versus manually administered epinephrine for the management of anaphylaxis. The guideline recommends the administration of epinephrine for immediate management of adults experiencing anaphylaxis (Level IV evidence, Grade C recommendation). The guidelines state that diagnosis must be rapid, with epinephrine administered early and at the appropriate dose in order to optimize outcomes (Level V evidence, Grade D recommendation). Potential allergens which may be the trigger to the anaphylaxis should be ceased as soon as possible (Level V evidence, Grade D recommendation). This is especially important in the case of refractory anaphylaxis (Level V evidence, Grade D recommendation). The guidelines state that patients should be returned to the supine positions as soon as possible, and a leg elevation should be considered when hypotension is prominent (Level IV evidence, Grade D recommendation). Aggressive fluid resuscitation is recommended (Level IV evidence, Grade D recommendation). The benefits of IM epinephrine for the management of anaphylaxis were found to outweigh the risks (Level I evidence), and the guidelines recommend IM administration in the initial management of perioperative anaphylaxis when IV access has not yet been established or is lost, where hemodynamic monitoring is not in place at the start of the reaction, or while waiting for an epinephrine infusion (Level 1 evidence, Grade B recommendation). Dose intervals of five minutes is recommended (Level V evidence, Grade D recommendation). The guidelines further recommend initial use of an IV bolus of epinephrine (Grade D recommendation). The guidelines recommend the use of an epinephrine infusion after three boluses of either IV or IM epinephrine have been administered (Level III evidence, Grade D recommendation). The guidelines state that there is little evidence to inform the immediate management of anaphylaxis in pediatric patients, and the scientific rationale for management in these patients is essentially the same as for adults.

For management of refractory anaphylaxis in adults, the ANZCA/ANZAAG guidelines1 recommend obtaining an arterial line where possible (Grade D recommendation), and the use of ultrasound to diagnose pneumothorax (Grade D recommendation). Cardiac bypass or extracorporeal membrane oxygenation can be considered to re-establish adequate perfusion (Grade D recommendation). The guidelines state that alternative vasopressors should only be considered following appropriate administration of epinephrine and IV fluids (Level V evidence, Grade D recommendation), and glucagon can be included in the management of resistant hypotension (Level V evidence, Grade D recommendation). In cases of resistant bronchospasm, salbutamol can be administered (Level V evidence, Grade D recommendation). Alternatively, IV magnesium or inhalation anesthetics and ketamine can be administered (Level V evidence, Grade D recommendation). For pregnant patients, manual left uterine displacement positioning is recommended in situations where the uterus is above the umbilicus (Level V evidence, Grade D recommendation). The guidelines further recommend that in the case of cardiac arrest, peri-mortem caesarean delivery should be performed (Level V evidence, Grade D recommendation).

For management of refractory anaphylaxis in pediatrics, the ANZCA/ANZAAG guidelines1 recommend first requesting advice and/or more assistance (Grade D recommendation). IV aminophylline and hydrocortisone are recommended along with inhaled salbutamol and IV magnesium recommendations (Grade D recommendation).

Relevant to this report, the JTFPP guidelines12 did not make any explicit distinction or recommendation for EAI versus manually administered epinephrine for the management of anaphylaxis. The guidelines provide 79 summary statement recommendations covering the 11 overall topics. These recommendations cover both diagnosis and management of anaphylaxis in different situations. Most recommendations focus on recognizing triggers and supplying the patients with education for the condition (various levels of recommendation and evidence). For in-office management of anaphylaxis, the guidelines recommend: 1) administering epinephrine IM (administration method not specified), 2) removing the allergen, assessing airway, breathing, circulation, and mentation and summoning appropriate assistance from staff members, and 4) starting, if needed, cardiopulmonary resuscitation and summoning emergency medical services. These were strong Recommendations based on level D Evidence.

Limitations

Several limitations must be considered when reviewing this report. The guidelines were released in the Unites States,12 and in Australia and New Zealand,1 and therefore their relevance to the Canadian context is unclear. Furthermore, neither guideline made recommendations as to whether an EAI or manual draw-up of epinephrine would be more favourable for health care practitioners in face of anaphylaxis. The guideline methodology was unclear, and the completeness of the evidence-search cannot be thoroughly analyzed.

Conclusions and Implications for Decision or Policy Making

No evidence was identified regarding the clinical effectiveness or cost-effectiveness of epinephrine auto-injectors compared to manually administered epinephrine for the management of individuals with anaphylaxis. Although no studies were identified that directly compared EAI versus manually administered epinephrine, two simulation studies6,13 in which radiology healthcare professionals participated in simulated anaphylaxis scenarios demonstrated that EAI administration was quicker and had less administration errors than manual epinephrine delivery. Whether these findings extend to real-life anaphylaxis situations is unknown.

Two evidence-based guidelines1,12 were identified that provide recommendations regarding the management of anaphylaxis. The guidelines present recommendations for various anaphylaxis situations, and they generally recommend and support the use of epinephrine for anaphylaxis. Neither guideline explicitly recommends any particular modality of epinephrine administration (i.e., EAI versus manual draw-up of epinephrine) by health care professionals. Both guidelines included systematic literature searches to inform the recommendations, however it was noted that limited evidence existed, and therefore most of the recommendations were formulated by expert-consensus. While one of the guidelines12 provided clear summary statements for the recommendations, the other guideline1 did not clearly present the included recommendations. Neither guideline1,12 was developed specifically for the Canadian context.

Overall, limited evidence was identified to address the research questions of this report. No clinical effectiveness studies or cost-effectiveness studies were identified; therefore, no conclusions can be drawn. Due to the life-threatening severity of anaphylaxis, RCTs directly investigating the clinical effectiveness of EAI versus manual delivery are likely unethical. As for the evidence-based guidelines, no recommendations were identified recommending one method of epinephrine administration over the other. Therefore, it may be too early to draw conclusions to support the use of EAI compared to manual delivery of epinephrine.

References

1.
Australian and New Zealand College of Anaesthetists, and Australian and New Zealand Anaesthetic Allergy Group. Perioperative anaphylaxis management guidelines. Melbourne, Australia: Australian and New Zealand College of Anaesthetists, Australian and New Zealand Anaesthetic Allergy Group; 2016 May.
2.
Sicherer SH, Simons FER. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139(3). [PubMed: 28193791]
3.
Kemp S. Pathophysiology of anaphylaxis. In: Post TW, ed. UpToDate. Waltham (MA): UpToDate; 2020 Mar: www​.uptodate.com. Accessed 2020 Apr 20.
4.
Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017;140(2):335–348. [PMC free article: PMC5657389] [PubMed: 28780941]
5.
Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020. [PubMed: 32001253]
6.
Restauri N, Lio E, Glueck D, et al. Best practice for safe and effective administration of epinephrine for the treatment of anaphylaxis in the radiology department. J Am Coll Radiol. 2016;13(3):303–306. [PubMed: 26499159]
7.
Sicherer S. Prescribing epinephrine for anaphylaxis self-treatment. In: Post TW, ed. UpToDate. Waltham (MA): UpToDate; 2020 Feb: www​.uptodate.com. Accessed 2020 Apr 20.
8.
El Turki A, Smith H, Llewellyn C, Jones CJ. A systematic review of patients’, parents’ and healthcare professionals’ adrenaline auto-injector administration techniques. Emerg Med J. 2017;34(6):403–416. [PubMed: 27466349]
9.
Lyng JW, White CC, Peterson TQ, et al. Non-auto-injector epinephrine administration by basic life support providers: a literature review and consensus process. Prehosp Emerg Care. 2019;23(6):855–861. [PubMed: 30917719]
10.
Consortium ANS. The AGREE II Instrument. [Hamilton, ON]: AGREE Enterprise; 2017: https://www​.agreetrust​.org/wp-content/uploads​/2017/12/AGREE-II-Users-Manual-and-23-item-Instrument-2009-Update-2017.pdf. Accessed 2020 Apr 20.
11.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–e34. [PubMed: 19631507]
12.
Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341–384. [PubMed: 26505932]
13.
Asch D, Pfeifer KE, Arango J, et al. Journal club: benefit of epinephrine autoinjector for treatment of contrast reactions: comparison of errors, administration times, and provider preferences. AJR: Am J Roentgenol. 2017;209(2):W363–w369. [PubMed: 28570127]

Appendix 1. Selection of Included Studies

Image app1f1

Appendix 2. Characteristics of Included Publications

Table 2Characteristics of Included Guidelines

Intended users, target populationIntervention and practice consideredMajor outcomes consideredEvidence collection, selection, and synthesisEvidence quality assessmentRecommendations development and evaluationGuideline validation
AANZCA-ANZAAG, 20161

Intended users: anaesthetists

Target population: patients experiencing perioperative anaphylaxis

Management of anesthetic anaphylaxis and general management of anaphylaxis

Evidence to inform the following recommendations (Relevant to this report): 1) immediate crisis in adults, 2) immediate crisis in pediatrics, 3) refractory management in adults, and 4) refractory management in pediatrics

The specific outcomes considered by the guideline development group were not explicitly reported

Published in 2016 as a revision to guidelines originally developed in 2013 by ANZAAG.

Systematic literature search was performed

Modified version of the NHMRC levels of evidence: Level 1 (highest) to Level V (lowest)a

Recommendations developed by consensus (as no relevant RCTs were identified)

Recommendations evaluated with NHMRC grades of recommendation: “A” (strongest) to “D” (weakest)a

The recommendation evaluations were taken from published reviews and other guidelines for the management of anaphylaxis.

None reported
JTFPP, 201512

Intended users: practicing physicians

Target population: patients experiencing anaphylaxis (not explicitly stated)

Diagnosis and management of anaphylaxis

Evidence-to inform the following: 1) Evaluation and Management of Patients with a History of Anaphylaxis, 2) Office Management of Anaphylaxis, 3) Anaphylaxis to Foods, 4) Anaphylaxis to Drugs and Biological Agents, 5) Insect Sting Anaphylaxis, 6) Perioperative Anaphylaxis: Anaphylaxis before, during, or Immediately after Anesthesia, 7) Seminal Fluid Anaphylaxis, 8) Exercise-induced Anaphylaxis, 9) Anaphylaxis to Subcutaneous AIT Extract (vaccine), 10) Anaphylaxis in Mastocytosis, MMAS, and MCAS, and 11) Unusual Presentations of Anaphylaxis.

The specific outcomes considered by the guideline development group were not explicitly reported

Published in 2015 as an update from the previously published 2010 parameters.

Systematic literature search was performed in PubMed, CENTRAL, Google Scholar, and Science Direct.

Unreferenced classification guide: “A” (strongest) to “D” (weakest)b

Evidence from the systematic literature search results, in combination with consensus expert opinion and workgroup-identified supplementary documents identified by the workgroup

Recommendations evaluated with an unreferenced classification guide: “Strong recommendation” to “No recommendation”b

None reported

AIT = Allergen immunotherapy; ANZAAG = Australian and New Zealand Anesthetic Allergy Group; ANZCA = Australian and New Zealand College of Anaesthetists; CENTRAL = Cochrane Central Register of Controlled Trials; JTFPP = Joint Task Force on Practice Parameters; MCAS = Mast cell activating syndrome; MMAS = Monoclonal mast cell activating syndrome; NHMRC = National Health and Medical Research Council; RCT = randomized controlled trials.

a

Detailed description of Levels of Evidence (based on NHMRC levels) and NHMRC grades of recommendation in Appendix 4, Table 4.

b

Detailed description of the unreferenced recommendation guide in Appendix 4, Table 4.

Appendix 3. Critical Appraisal of Included Publications

Table 3Strengths and Limitations of Guidelines Using AGREE II10

ItemGuideline
AANZCA-ANZAAG, 20161JTFPP, 201512
Domain 1: Scope and Purpose
1. The overall objective(s) of the guideline is (are) specifically described.YesYes
2. The health question(s) covered by the guideline is (are) specifically described.YesYes
3. The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described.YesNo (but implied)
Domain 2: Stakeholder Involvement
4. The guideline development group includes individuals from all relevant professional groups.YesYes
5. The views and preferences of the target population (patients, public, etc.) have been sought.NRYes (Limited)
6. The target users of the guideline are clearly defined.YesYes
Domain 3: Rigour of Development
7. Systematic methods were used to search for evidence.YesYes
8. The criteria for selecting the evidence are clearly described.NoNo
9. The strengths and limitations of the body of evidence are clearly described.YesYes
10. The methods for formulating the recommendations are clearly described.NoNo
11. The health benefits, side effects, and risks have been considered in formulating the recommendations.NRNR
12. There is an explicit link between the recommendations and the supporting evidence.YesYes
13. The guideline has been externally reviewed by experts prior to its publication.NRNR
14. A procedure for updating the guideline is provided.YesNR
Domain 4: Clarity of Presentation
15. The recommendations are specific and unambiguous.NoYes
16. The different options for management of the condition or health issue are clearly presented.YesYes
17. Key recommendations are easily identifiable.YesYes
Domain 5: Applicability
18. The guideline describes facilitators and barriers to its application.NRNR
19. The guideline provides advice and/or tools on how the recommendations can be put into practice.YesNR
20. The potential resource implications of applying the recommendations have been considered.NRNR
21. The guideline presents monitoring and/or auditing criteria.NRYes
Domain 6: Editorial Independence
22. The views of the funding body have not influenced the content of the guideline.NRYes
23. Competing interests of guideline development group members have been recorded and addressed.NRYes

ANZAAG = Australian and New Zealand Anesthetic Allergy Group; ANZCA = Australian and New Zealand College of Anaesthetists; JTFPP = Joint Task Force on Practice Parameters; NR = not reported.

Note: “Not reported” indicates there was insufficient detail provided to be able to firmly conclude the AGREE II criteria was or was not met.

Appendix 4. Main Study Findings and Authors’ Conclusions

Table 4. Summary of Recommendations in Included Guidelines (PDF, 258K)

Appendix 5. Additional References of Potential Interest

Guidelines with Unclear Methodology

1.
ASCIA guidelines: acute management of anaphylaxis. Australasian Society of Clinical Immunology and Allergy; 2019: https://www​.allergy.org​.au/images/stories​/pospapers/ASCIA_Guidelines​_Acute_Management​_Anaphylaxis_2019.pdf Accessed 2020 Apr 20.
2.
BC Centre for Disease Control. Communicable disease control Manual: chapter 2: immunization. Part 3 - management of anaphylaxis in a non-hospital setting; 2019 Feb: http://www​.bccdc.ca/resource-gallery​/Documents​/Guidelines%20and%20Forms​/Guidelines%20and%20Manuals​/Epid​/CD%20Manual/Chapter%202%20-%20Imms​/Part_3_Anaphylaxis​.pdf Accessed 2020 Apr 20.

Related CADTH Reports

1.
Epinephrine auto-injector availability in public settings: clinical effectiveness and guidelines (Rapid response report: summary of abstracts). Ottawa (ON): CADTH; 2015 Mar: https://www​.cadth.ca​/sites/default/files​/pdf/htis/mar-2015/RB0803​%20Public%20Epinephrine​%20Auto-injector%20Final.pdf Accessed 2020 Apr 20.
2.
Higher than recommended doses of epinephrine for patients with an allergic reaction: clinical evidence and safety (Rapid response report: summary of abstracts). Ottawa (ON): CADTH; 2011 May: https://www​.cadth.ca​/sites/default/files​/pdf/htis/may-2011/RB0354​_EpinephrineDosing_Final.pdf Accessed 2020 Apr 20.
3.
Different routes of epinephrine for anaphylaxis: clinical efficacy. Ottawa (ON): CADTH; 2008 Jan: https://www​.cadth.ca​/sites/default/files​/pdf/htis/Different%20Routes​%20of%20Epinephrine​%20for%20Anaphylaxis​%20Clinical%20Efficacy.pdf Accessed 2020 Apr 20.

About the Series

CADTH Rapid Response Report: Summary with Critical Appraisal
ISSN: 1922-8147

Version: 1.0

Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.

Suggested citation:

Epinephrine auto-injectors for anaphylaxis: a review of the clinical effectiveness, cost-effectiveness, and guidelines. Ottawa: CADTH; 2020 Apr. (CADTH rapid response report: summary with critical appraisal).

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