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. 2008 Oct 8;2008(4):CD006312.
doi: 10.1002/14651858.CD006312.pub2.

Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock

Aziz Sheikh  1 , Yasser A Shehata, Simon Ga Brown, F Estelle R Simons
Affiliations

Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock

Aziz Sheikh et al. Cochrane Database Syst Rev. .

Abstract

Background: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis.

Objectives: To assess the benefits and harms of adrenaline (epinephrine) in the treatment of anaphylaxis.

Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/; and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material.

Selection criteria: Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion.

Data collection and analysis: Two authors independently assessed articles for inclusion.

Main results: We found no studies that satisfied the inclusion criteria.

Authors' conclusions: 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.

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Conflict of interest statement

Aziz Sheikh:has obtained funding from ALK‐Abello to support conference attendance by members of our research group.

Yasser A Shehata, Simon GA Brown and F Estelle R Simons: none known.

Figures

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Search flow diagram
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References

Additional references

Alrasbi 2007
    1. Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy 2007;62:838‐41. - PubMed
Alves 2001
    1. Alves B, Sheikh A. Age specific aetiology of anaphylaxis. Archives of Disease in Childhood 2001;85:348. - PMC - PubMed
Bautista 2002
    1. Bautista E, Simons FER, Simons KJ, Becker AB, Duke K, Tillett M, et al. Epinephrine fails to hasten hemodynamic recovery in fully developed canine anaphylactic shock. International Archives of Allergy and Applied Immunology 2002;128:151‐64. - PubMed
Begg 1994
    1. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088‐101. - PubMed
Bock 2001
    1. Bock SA, Munoz‐Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. The Journal of Allergy and Clinical Immunology 2001;107:191‐3. - PubMed
Bock 2007
    1. Bock SA, Munoz‐Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001‐2006. The Journal of Allergy and Clinical Immunology 2007;119:1016‐8. - PubMed
Bohlke 2004
    1. Bohlke K, Davis RL, DeStefano F, Marcy SM, Braun MM, Thompson RS, Vaccine Safety Datalink Team. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. The Journal of Allergy and Clinical Immunology 2004;113:536‐42. - PubMed
Brown 1998
    1. Brown AFT. Therapeutic controversies in the management of acute anaphylaxis. Journal of Accident & Emergency Medicine 1998;15:89‐95. - PMC - PubMed
Brown 2001
    1. Brown AF, McKinnon D, Chu K. Emergency department anaphylaxis: a review of 142 patients in a single year. The Journal of Allergy and Clinical Immunology 2001;108:861‐6. - PubMed
Brown 2004a
    1. Brown SG, Blackman KE, Stenlake V, Heddle RJ. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emergency Medicine Journal 2004;21:149‐54. - PMC - PubMed
Brown 2004b
    1. Brown SG. Clinical features and grading of anaphylaxis. The Journal of Allergy and Clinical Immunology 2004;114:371‐6. - PubMed
Brown 2005
    1. Brown SGA. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Current Opinion in Allergy and Clinical Immunology 2005;5:359‐64. - PubMed
Brown 2006
    1. Brown SG. Anaphylaxis: clinical concepts and research priorities. Emergency Medicine Australasia 2006;18:155‐69. - PubMed
Chamberlain 1999
    1. Chamberlain D. Emergency medical treatment of anaphylactic reactions. Project team of the resuscitation council (UK). Journal of Accident & Emergency Medicine 1999;16:243‐7. - PMC - PubMed
Clark 2006
    1. Clark S, Gaeta TJ, Kamarthi GS, Camargo CA. ICD‐9‐CM coding of emergency department visits for food and insect sting allergy. Annals of Epidemiology 2006;16:696‐700. - PubMed
Dec Helsinki 1996
    1. World Health Organization. Declaration of Helsinki. BMJ 1996;313:1448‐9.
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐ analysis detected by a simple, graphical test. BMJ 1997;315:629‐34. - PMC - PubMed
Fischer 1995
    1. Fischer M. Fortnightly review: treatment of acute anaphylaxis. BMJ 1995;311:731‐3. - PMC - PubMed
Fisher 1978
    1. Fisher MM. Acute life‐threatening reactions to contrast media. Aust Radiol 1978;22:365‐71. - PubMed
Greenberger 2007
    1. Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Annals of Allergy, Asthma & Immunology 2007;98:252‐7. - PubMed
Hebling 2004
    1. Helbling A, Hurni T, Mueller UR, Pichler WJ. Incidence of anaphylaxis with circulatory symptoms: a study over a 3‐year period comprising 940,000 inhabitants of the Swiss Canton Bern. Clinical and Experimental Allergy 2004;34:285‐90. - PubMed
Heilborn 1986
    1. Heilborn H, Hjemdahl P, Daleskog M, Adamsson U. Comparison of subcutaneous injection and high‐dose inhalation of epinephrine ? implications for self‐treatment to prevent anaphylaxis. Journal of Allergy and Clinical Immunology 1986;76:1174‐9. - PubMed
Higgins 2002
    1. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21:1539‐58. - PubMed
Higgins 2009
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.
Johansson 2001
    1. Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel‐Koomen C, Dreborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001;56:813‐24. - PubMed
Johansson 2004
    1. Johansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. The Journal of Allergy and Clinical Immunology 2004;113:832‐6. - PubMed
Johnston 2003
    1. Johnston SL, Unsworth J, Gompels M. Adrenaline given outside the context of life threatening allergic reactions. BMJ 2003;326:589‐90. - PMC - PubMed
Kemp 2002
    1. Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. The Journal of Allergy and Clinical Immunology 2002;110:341‐8. - PubMed
Klein 1995
    1. Klein JS, Yocum MW. Underreporting of anaphylaxis in a community emergency room. The Journal of Allergy and Clinical Immunology 1995;95:637‐8. - PubMed
Kounis 2006
    1. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm?. International Journal of Cardiology 2006;110:7‐14. - PubMed
Lieberman 2003
    1. Lieberman PL. Anaphylaxis and anaphylactoid reactions. Middleton's Allergy: Principles and Practice, 6th edition. Mosby, 2003.
Lieberman 2006
    1. Lieberman P, Camargo C, Bohlke K, Jick H, Miller R, Sheikh A, et al. Epidemiology of anaphylaxis: findings of the ACAAI Epidemiology of Anaphylaxis Working Group. Annals of Allergy, Asthma & Immunology 2006;97:596‐602. - PubMed
Lin 2000
    1. Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department‐based study. The Journal of Allergy and Clinical Immunology 2000;106:65‐71. - PubMed
Marone 2004
    1. Marone G, Bova M, Detoraki A, Onorati AM, Rossi FW, Spadaro G. The human heart as a shock organ in anaphylaxis. Novartis Foundation Symposium 2004;257:133‐49. - PubMed
McLean‐Tooke 2003
    1. McLean‐Tooke AP, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence?. BMJ 2003;327:1332‐5. - PMC - PubMed
Mink 2004
    1. Mink SN, Simons FER, Simons KJ, Becker AB, Duke K. Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology 2004;34:1776‐83. - PubMed
Montanaro 2002
    1. Montanaro A, Bardana EJ Jr. The mechanisms, causes and treatment of anaphylaxis. Journal of Investigational Allergology & Clinical Immunology 2002;1:2‐11. - PubMed
Muller 2007
    1. Muller U. Cardiovascular disease and anaphylaxis. Current Opinion in Allergy and Clinical Immunology 2007;7:337‐41. - PubMed
Neugut 2001
    1. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Archives of Internal Medicine 2001;161:15‐21. - PubMed
Peng 2004
    1. Peng MM, Jick H. A population‐based study of the incidence, cause, and severity of anaphylaxis in the United Kingdom. Archives of Internal Medicine 2004;164:317‐9. - PubMed
Pumphrey 2000
    1. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology 2000;30:1144‐50. - PubMed
Pumphrey 2007
    1. Pumphrey RSH, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999‐2006. The Journal of Allergy and Clinical Immunology 2007;119:1018‐9. - PubMed
RevMan 5.0 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Sampson 1992
    1. Sampson HA, Mendelson L, Rosen JP. Fatal and near‐fatal anaphylactic reactions to food in children and adolescents. The New England Journal of Medicine 1992;327:380‐4. - PubMed
Sampson 2005
    1. Sampson HA, Munoz‐Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA, et al. Symposium on the definition and management of anaphylaxis: summary report. The Journal of Allergy and Clinical Immunology 2005;115:584‐91. - PubMed
Sampson 2006
    1. Sampson HA, Munoz‐Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report. Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. The Journal of Allergy and Clinical Immunology 2006;117:391‐7. - PubMed
Sheikh 2001
    1. Sheikh A, Alves B. Age, sex, geographical and socio‐economic variations in admissions for anaphylaxis: analysis of four years of English hospital data. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology 2001;31:1571‐6. - PubMed
Sicherer 2005
    1. Sicherer SH, Simons FER. Quandaries in prescribing an emergency action plan and self‐injectable epinephrine for first‐aid management of anaphylaxis in the community. The Journal of Allergy and Clinical Immunology 2005;115:575‐83. - PubMed
Simons 1998
    1. Simons FER. Epinephrine absorption in children with a history of anaphylaxis. Journal of Clinical Immunology 1998;101:33‐7. - PubMed
Simons 2000
    1. Simons FER, Gu X, Johnston L, Simons KJ. Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?. Pediatrics 2000;106:1040‐4. - PubMed
Simons 2001
    1. Simons FER, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. The Journal of Allergy and Clinical Immunology 2001;108:871‐3. - PubMed
Simons 2002a
    1. Simons FER, Peterson S, Black CD. Epinephrine dispensing patterns for an out‐of‐hospital population: a novel approach to studying the epidemiology of anaphylaxis. The Journal of Allergy and Clinical Immunology 2002;110:647‐51. - PubMed
Simons 2002b
    1. Simons FER, Chad ZH, Gold M. Real‐time reporting of anaphylaxis in infants, children and adolescents by physicians involved in the Canadian Pediatric Surveillance Program. The Journal of Allergy and Clinical Immunology 2002;109 Suppl:181.
Simons 2004
    1. Simons FER. First‐aid treatment of anaphylaxis to food: Focus on epinephrine. The Journal of Allergy and Clinical Immunology 2004;113:837‐44. - PubMed
Simons 2006
    1. Simons FER. Anaphylaxis, killer allergy: Long‐term management in the community. The Journal of Allergy and Clinical Immunology 2006;117:367‐77. - PubMed
Simons 2007a
    1. Simons FER, Frew AJ, Ansotegui IJ, Bochner BS, Finkelman F, Golden DBK, et al. Risk assessment in anaphylaxis: current and future approaches. The Journal of Allergy and Clinical Immunology 2007;120 Suppl:2‐24. - PubMed
Simons 2007b
    1. Simons FE, Sheikh A. Evidence‐based management of anaphylaxis. Allergy 2007;62:827‐9. - PubMed
Simons 2008
    1. Simons FER. Emergency treatment of anaphylaxis: Revised UK guidelines are a concise evidence based resource. British Medical Journal 2008;336:1141‐2.
Soar 2008
    1. Soar J, Pumphrey R, Cant A, et al. for the Working Group of the Resuscitation Council (UK). Emergency treatment of anaphylactic reactions: Guidelines for healthcare providers. Resuscitation 2008;77:157‐69. - PubMed
Yocum 1999
    1. Yocum MW, Butterfield JH, Klein JS, Volcheck GW, Schroeder DR, Silverstein MD. Epidemiology of anaphylaxis in Olmsted County: A population‐based study. The Journal of Allergy and Clinical Immunology 1999;104:452‐6. - PubMed

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