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Second dose of epinephrine for anaphylaxis

Question Type:
Intervention
Full Question:
Among adults and children experiencing anaphylaxis requiring the use of epinephrine

 (P), does administration of a second dose of epinephrine

 (I), compared to administration of only one dose

 (C), change resolution of symptons, adverse effects, complications (O)?
Consensus on Science:
For the critical outcome of resolution of symptoms, we identified very-low-quality evidence (downgraded for risk of bias and confounding) from 9 observational studies(Korenblat 1999, 383; Oren 2007, 429; Jarvinen 2008, 133; Banerji 2010, 308-316; Rudders 2010, e711-e718; Rudders 2010, 85; Noimark 2012, 284; Inoue 2013, 106; Tsuang 2013, AB90) showing benefit for giving a second dose (or multiple doses) of epinephrine to patients not responding to a first dose (RR, 1.16; 95% CI, 1.13–1.20).In addition, for the critical outcome of resolution of symptoms, we identified very-low-quality evidence (downgraded for risk of bias) from 1 observational study(Ellis 2013, S146) showing no significant difference between the percentage of resolved reactions in an ambulance service routinely using 2 doses of epinephrine versus an ambulance service using a single dose (RR, 0.97; 95% CI, 0.9–1.04).We did not identify any evidence to address the critical outcomes of adverse effects or complications.
Treatment Recommendation:
We suggest a second dose of epinephrine be administered by autoinjector to individuals with severe anaphylaxis whose symptoms are not relieved by an initial dose (weak recommendation, very-low-quality evidence). Values, Preferences, and Task Force InsightsIn making this recommendation, we place a higher value on the resolution of life-threatening symptoms, such as airway compromise, breathing difficulty, and circulatory collapse, over the potential risk of adverse effects from an unnecessary second injection. When caring for a person with anaphylaxis, first aid providers should always call for 9-1-1 EMS. Public comments and discussion on this topic centered on issues of dosing, interval time for a second dose, and the possibility of adverse effects should epinephrine be inadvertently administered to a person not experiencing anaphylaxis. This evidence review did not evaluate the time interval between doses of epinephrine or the optimal dose. However, literature included in the review suggests that a second dose of epinephrine may be administered 10 to 15 minutes after the initial dose.(Korenblat 1999, 383) While the included studies did not identify any adverse effects, selection bias might have prevented those effects from being identified. Adverse effects have previously been reported in the literature when epinephrine is administered in the incorrect dose or via inappropriate routes, such as the intravenous route. Use of autoinjectors by first aid providers may minimize the opportunity for incorrect dosing of epinephrine.
CoSTR Attachments:
20150115_GRADE table_Second dose epinephrine final_n.docx    

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