Epinephrine (adrenaline) in the first-aid, out-of-hospital treatment of anaphylaxis.

Epinephrine (adrenaline), the initial treatment of choice for systemic anaphylaxis, is an alpha- and beta-adrenergic agonist with bidirectional, cyclic adenosine monophosphate-mediated pharmacological effects on target organs, and a narrow therapeutic index. In a recent study, 0.95% of a geographically-defined population was found to have had epinephrine dispensed for out-of-hospital use; dispensing rates within this population varied from 1.44% for individuals under age 17 years to 0.32% for those older than 65 years. Although epinephrine is widely available in the community, it is not necessarily given in a timely manner when anaphylaxis occurs. Individuals with anaphylaxis may fail to respond to first-aid treatment with epinephrine for a variety of reasons. These include: (1) delay in treatment (in an animal model, epinephrine injection at the nadir of shock fails to provide sustained haemodynamic recovery); (2) administration of epinephrine by sub-optimal routes such as subcutaneous injection or inhalation from a pressurized metered-dose inhaler instead of intramuscular injection; (3) administration of an inappropriately low epinephrine dose due to the limitations currently imposed by the availability of only two fixed-dose auto-injectors: EpiPen Jr 0.15 mg or EpiPen 0.3 mg; and (4) injection of 'outdated' epinephrine, with inadvertent administration of an inadequate dose. Additional fixed-dose formulations of epinephrine are needed to facilitate optimal first-aid dosing in patients of all ages and sizes.