Adrenaline auto-injectors for the treatment of anaphylaxis in the community

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. It is commonly triggered by a food, insect sting, medication, or natural rubber latex. The reaction typically occurs without warning and can be a frightening and life-threatening experience for those at risk and for their families and friends. Adrenaline (epinephrine) is widely advocated as the main treatment in people experiencing anaphylaxis and many people at risk of anaphylaxis are prescribed adrenaline auto-injectors (such as the Adrenaclick, Anapen, Epipen, Jext, and Twinject) so that they or their families can, if needed, administer adrenaline in the community. Potential problems with adrenaline auto-injector use include failure to carry the auto-injector at all times; failure to use it because the signs and symptoms of anaphylaxis are not recognized; a preference to use an oral antihistamine; or fear and panic in the emergency. In addition, in many countries adrenaline auto-injectors are either not available or they are not affordable. The evidence base regarding the effectiveness of adrenaline auto-injectors is unclear. We therefore conducted a systematic review of the literature, searching key databases for high quality published and unpublished material on the use of adrenaline auto-injectors during episodes of anaphylaxis in the community. We also contacted the relevant pharmaceutical companies to see if they had any such information on the topic. Our searches found many studies relating to anaphylaxis and adrenaline auto-injector use but no randomized controlled trials on this subject. We concluded that the use of adrenaline auto-injectors in anaphylaxis is based on the best available information at present. There is no evidence from randomized controlled trials for the effectiveness of adrenaline auto-injectors in the emergency treatment of anaphylaxis in the community. Such trials would ideally involve comparison of adrenaline with placebo; however, use of a placebo in anaphylaxis treatment would be unethical. We therefore recommend that auto-injectors remain the medication of first choice in the treatment of anaphylaxis in the community.

Authors' conclusions: 

Based on this review, we cannot make any new recommendations on the effectiveness of adrenaline auto-injectors for the treatment of anaphylaxis. Although randomized, double-blind, placebo-controlled clinical trials of high methodological quality are necessary to define the true extent of benefits from the administration of adrenaline in anaphylaxis via an auto-injector, such trials are unlikely to be performed in individuals experiencing anaphylaxis because of ethical concerns associated with randomization to placebo. There is, however, a need to consider trials in which, for example, auto-injectors of different doses of adrenaline and differing devices are compared in order to provide greater clarity on the dose and device of choice. Such trials would be practically challenging to conduct. In the absence of appropriate trials, we recommend that adrenaline administration by auto-injector should still be regarded as the most effective first-line treatment for the management of anaphylaxis in the community. In countries where auto-injectors are not commonly used, it may be possible to conduct trials to compare administration of adrenaline via auto-injector with adrenaline administered by syringe and ampoule, or comparing the effectiveness of two different types of auto-injector.

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Background: 

Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline (epinephrine) auto-injectors are recommended as the initial, potentially life-saving treatment of choice for anaphylaxis in the community, but they are not universally available and have limitations in their use.

Objectives: 

To assess the effectiveness of adrenaline (epinephrine) auto-injectors in relieving respiratory, cardiovascular, and other symptoms during episodes of anaphylaxis that occur in the community.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1950 to January 2012), EMBASE (Ovid SP) (1980 to January 2012 ), CINAHL (EBSCO host) (1982 to January 2012 ), AMED (EBSCO host) (1985 to January 2012 ), LILACS, (BIREME) (1980 to January 2012 ), ISI Web of Science (1950 to January 2012 ). We adapted our search terms for other databases. We also searched websites listing on-going trials: the World Health Organization International Clinical Trials Registry Platform, the UK Clinical Research Network Study Portfolio, and the meta Register of Controlled Trials; and contacted pharmaceutical companies who manufacture adrenaline auto-injectors in an attempt to locate unpublished material.

Selection criteria: 

Randomized and quasi-randomized controlled trials comparing auto-injector administration of adrenaline with any control including no intervention, placebo, or other adrenergic agonists were eligible for inclusion.

Data collection and analysis: 

Two authors independently assessed articles for inclusion.

Main results: 

None of the 1328 studies that were identified satisfied the inclusion criteria.

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