Thank you for your inquiry.
As a preface, there is no information available, to my knowledge, as to how a suggested dose of 0.01 mg per kilogram to treat anaphylaxis was derived. There are, to my knowledge, no dose response studies of epinephrine administration either in children or adults. I have heard "tales" as to how this dose was derived, but have never been able to find any published data in the medical literature to substantiate that this is indeed "the correct dose."
This model was, of course, used to establish the dosing in automatic epinephrine injectors, but, as you can see, there is no true indication that this dose is correct; and in fact, when one looks at previous suggested doses for epinephrine in adults, the dose of 0.3 mg (the suggested adult dose for automatic epinephrine injectors) is far lower than previous doses that have been suggested. A dose as high as 1 mg has been suggested for the treatment of asthma in the past, and before the advent of the automatic epinephrine injector, the dose for treatment of anaphylaxis was 0.5 mg.
Thus, as best I can tell, there is no true scientific validation of the dosing suggested in the package insert. At least I can find none with a literature search.
Knowing this, and also knowing that the indication for an automatic epinephrine injector is any patient who is "at risk of an anaphylactic event," in my opinion, it is a better choice to prescribe an automatic epinephrine injector to children under 33 pounds than to allow them to be devoid of treatment should an event occur. Children are usually quite tolerant to the administration of epinephrine and, in my personal assessment, the risk is far greater from the event than the administration of a dose that is higher than 0.01 mg per kilogram in a child.
I also feel, based upon work by Estelle Simons, et al., that it is better to prescribe an automatic epinephrine injector in these children than to try to teach the parent how to administer a dose of 0.01 mg per kilogram using a syringe and vial (1).
If you are interested also in further discussions of the issues mentioned here, there are two other articles which you might find helpful (2, 3).
Thank you again for your inquiry and we hope this response is helpful to you.
1. Simons FER, et al. Epinephrine for the out of hospital (first-aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical? J Allergy Clin Immunol 2001; 106(6):100-1044.
2. Sicherer and Simons. Quandaries in prescribing an emergency action plan in self-injectable epinephrine for first-aid management of anaphylaxis in the community. J Allergy Clin Immunol 2005; 115(3):575-583.
3. Lieberman P. The 10 second rule and other myths about epinephrine and autoinjectors. Annals of Allergy, Asthma and Immunology 2011; 107(3):189-190.
Phil Lieberman, M.D.