Comparison of subcutaneous injection and high-dose inhalation of epinephrine--implications for self-treatment to prevent anaphylaxis

Abstract

The plasma concentrations of epinephrine were determined in healthy subjects administered epinephrine by subcutaneous injection of 0.5 mg or inhalation of 1.5 to 4.5 mg (10 to 30 inhalations from a metered-dose aerosol). The absorption of injected epinephrine was variable and in several cases very slow. The individual maximum values for epinephrine in plasma were 4.65 +/- 1.09 (range 0.74 to 8.31) nmol/L, and these maxima were attained 5 to 120 minutes after injection. Inhaled epinephrine was rapidly and dose dependently absorbed. Ten inhalations resulted in 2.72 +/- 0.84 (0.75 to 5.67) nmol/L within 5 minutes and 20 inhalations resulted in 7.19 +/- 1.78 (2.10 to 13.83) nmol/L with rapid increases and maxima within 20 minutes in seven of eight subjects. Gastrointestinal side effects were dose limiting when epinephrine was administered by inhalation. Our results indicate that inhalation of 2 to 3 mg of epinephrine produces rapid increases of epinephrine concentrations in plasma to levels that have previously been demonstrated to counteract bronchoconstriction induced by inhaled allergen in subjects with asthma. Inhalation has several advantages over injection for self-administration of epinephrine, e.g., in patients who are allergic to insect (Hymenoptera) stings. Apart from the absorption being more rapid, the locally high concentrations of epinephrine in the airways should be advantageous, since bronchoconstriction is one of the life-threatening phenomena of the anaphylactic reaction. This route of administration is also simple for the patient.