Treatment of persons with systemic anaphylaxis is most often accomplished with an intramuscular injection of epinephrine. This route of administration allows rapid absorption, and peak plasma concentrations and systemic effects occur promptly. However, many children with a history of anaphylaxis do not always carry injectable epinephrine with them. Epinephrine administered through a metered-dose inhaler is an acceptable alternative and is recommended worldwide. The cost is low, it is noninvasive, available without a prescription in many countries and not usually associated with adverse effects. Simons and associates conducted a prospective, randomized, placebo-controlled, parallel group trial to determine whether metered-dose inhalation is a feasible method of administering epinephrine in children at risk for anaphylaxis.
Children between the ages of six and 14 years were included if they had a history of allergies or anaphylaxis, and carried injectable epinephrine with them. Children were excluded if they had a history of hypertension, heart disease, seizures or other neurologic disorders, and if they were unable to discontinue the use of adrenergic drugs for at least 24 hours before the study. They had to agree to avoid methylx-anthine-containing agents (e.g., chocolate, cocoa, cola) for 24 hours before the study and for the duration of the study. Patients were allowed to take low-dose inhaled or intranasal glucocorticoids during the study. Blood pressure, heart rate and heart rhythm were monitored for each participant at baseline, and the ability of the child to use a metered-dose inhaler was assessed. Nineteen children were randomized to receive either inhaled epinephrine (0.5 percent solution, delivering approximately 0.25 mg via a mouthpiece) or placebo. The prescribed dosage was 10 inhalations within two minutes for children weighing between 20 and 30 kg (44 to 66 lb), 15 inhalations within three minutes for children weighing from 30 to 40 kg (66 to 88 lb) and 20 inhalations within four minutes for children weighing more than 40 kg (88 lb). The actual number of inhalations and the elapsed time were recorded. Blood samples were obtained at baseline and 10 times after the inhalations during the next three hours to determine the blood glucose and plasma epinephrine concentrations. Blood pressure and heart rate were also monitored.
Nine of 11 children in the epinephrine group and six of eight children in the placebo group had a history of asthma and had previously used a metered-dose inhaler. Nonetheless, only two of 11 children in the epinephrine group and two of eight in the placebo group achieved 100 percent of the inhalations theoretically needed to achieve a significant elevation in epinephrine concentration. Mean plasma epinephrine and blood glucose concentration levels were higher in the epinephrine group. Mean systolic blood pressure was also higher in the treatment group, although heart rate and diastolic blood pressure did not differ significantly between groups. Adverse effects (primarily bad taste of the inhalant) were experienced by 10 of 11 children in the treatment group and four of eight children in the placebo group. During inhalation, coughing occurred in two of 11 children in the epinephrine group and four of eight children in the placebo group. Three children in each group experienced dizziness. The overall dosage of epinephrine inhaled was 2.64 +/− 0.41 mg, a dosage that is about 10 times higher than the 0.3 mg that is usually given via injection.
The authors conclude that inhaled epinephrine is not a feasible alternative to injectable epinephrine and should not be recommended for pediatric patients experiencing systemic anaphylaxis.