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Report by Richard Body, Specialist Registrar in Emergency Medicine
Checked by Deepak Doshi, Specialist Registrar in Emergency Medicine
Institution: Manchester Royal Infirmary, Manchester, UK
A short cut review was carried out to establish whether there is any evidence in favour of epinephrine self-injection for anaphylactic reactions in children. Only three papers provided evidence related to the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are presented in table 1. The clinical bottom line is that although there are no clinical trials to answer the question there is other evidence to suggest that it can be effective.
In [children with anaphylaxis] does [self-injection of epinephrine] lead to [reduced mortality and morbidity]?
A 5-year-old boy is admitted with anaphylactic shock having inadvertently ingested peanuts at a birthday party. He had a previous reaction 2 years ago and was given an epinephrine auto-injector for use at home. His mother had used this when the reaction first started, but to no avail. You administer intramuscular epinephrine while wondering whether there is any evidence for the effectiveness of epinephrine self-injection.
Ovid Medline 1950–2007 August week 5; Ovid Embase 1980–2007 week 35; The Cochrane Library 2007, Issue 3.
Medline, Embase: [exp Anaphylaxis/OR anaphyla$.mp. OR exp Hypersensitivity/OR allerg$.mp.] AND [epipen.mp. OR epi-pen.mp. OR “epi-EZ pen”.mp. OR “epi ez pen”.mp. OR ana-kit.mp. OR exp epinephrine/OR adrenaline.mp.] AND [(exp Home Care Services/OR exp Outpatients/OR community.mp. OR out-patient$.mp. OR self-administr$.mp. OR home.mp. OR exp First Aid/OR first aid.mp.) OR (exp Infant Mortality/OR exp Child Mortality/OR mortality.mp. OR exp Hospital Mortality/OR exp Mortality/OR exp Death/OR exp “Cause of Death”/OR exp Death, Sudden/OR death.mp.)] AND limit to human and English language and All Child 0–18 years (Ovid filter).
Cochrane: ([MeSH heading Anaphylaxis] OR anaphyla*) AND ([MeSH heading Epinephrine] OR adrenaline OR epinephrine OR epipen)
Altogether 94 papers were identified using Medline, 585 using Embase and 26 using Cochrane. Three papers provided evidence that was relevant to the three part question (table 1).
Epinephrine is the drug of choice for initial treatment of severe anaphylaxis as it blocks mediator release and reverses systemic effects. Many children are now prescribed epinephrine auto-injectors for emergency use in the community.
The survey identified suggests that epinephrine self-injection may reduce subsequent hospital admission and need for epinephrine in hospital. However, it is notable that 76% of parents were not familiar with the correct procedure for using the devices, despite prior instruction (Gold et al, 2000).
There is evidence that prompt use of epinephrine improves prognosis in severe anaphylactic reactions. Sampson et al (1992) studied six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation. The six who died had symptoms within 3–30 min of allergen ingestion and only two received epinephrine within the first hour. All patients who survived had symptoms within 5 min of allergen ingestion and all but one received epinephrine within 30 min. Bock et al (2001) found that only four of 32 fatal anaphylactic reactions identified from a registry had received timely epinephrine.
As 53% of children with reported allergic reactions in the UK and Ireland between 1998 and 2000 (MacDougall et al, 2002) have had a previous allergic reaction (9% requiring hospitalisation), there is certainly potential to identify children who may be eligible for epinephrine self-treatment in the future. However, the number of patients who may benefit from widespread availability of epinephrine auto-injectors is likely to be small. A significant proportion of children will not have their auto-injector available at the time of the reaction. Others may be unfamiliar with the technique for self-injection, a small number may die despite treatment, and many patients have had no previous reaction (therefore being ineligible for prior epinephrine prescription).
It is known that epinephrine may lead to cardiac arrhythmia. Colver et al (2005) reported three cases where excess epinephrine administration in hospital was implicated in clinical deterioration. MacDougall et al (2002) reported one case in which death was attributed to excess intravenous epinephrine administration. However, the reported search strategy did not reveal any evidence of death or cardiac arrhythmia following self-injection of intramuscular epinephrine.
Although there is no evidence of high quality available to answer the three-part question, there is a sound physiological basis for the early use of epinephrine in severe anaphylaxis. At present it would be unethical to perform a randomised controlled trial. As early epinephrine may be life-saving and in the absence of evidence of harm following self-injection, measures to increase its availability should be encouraged even in the absence of high level evidence.
Clinical bottom line
Where available, epinephrine auto-injectors should be utilised in the community at an early stage for severe anaphylactic reactions, although high quality evidence is lacking. To maximise any potential benefit it is important to provide education for patients, parents and carers regarding injection technique and ensuring auto-injector availability at all times.
LEVEL OF EVIDENCE
Level 3—small numbers of small studies or great heterogeneity or very different population.