Simons FER, Gu X, Silver NA, Simons KJ. J Allergy Clin Immunol 2002;109:171–175
Purpose of the Study.
Epinephrine autoinjectors are widely prescribed for out-of-hospital treatment of children at risk for anaphylaxis. Prescribing physicians face the dilemma of choosing either the 0.15-mg EpiPen Jr or the 0.30-mg EpiPen when neither dose is deemed optimal. These investigators studied the rate and extent of epinephrine absorption after administration of either EpiPen Jr or EpiPen in children weighing 15 to 30 kg.
Ten children were recruited from pediatric allergy practices with the following entry criteria: age, 4 to 8 years; weight. 15 to 30 kg; history of severe acute allergic reaction(s); and current EpiPen Jr or EpiPen carriage. Eight patients had peanut anaphylaxis, while 1 each had anaphylaxis to egg and fish.
Study patients were randomly assigned in double-blind manner to self-administer either EpiPen Jr or EpiPen in the lateral thigh after formal review of proper administration technique. Plasma epinephrine concentrations, blood glucose, blood pressure, heart rate, and adverse effects were monitored before and for 180 minutes after the injection.
The 5 children who used EpiPen Jr had a mean age of 5.4 years, mean weight of 18.0 kg, and achieved a maximum plasma epinephrine concentration of 2037 pg/mL at 16 minutes. Those who used EpiPen had a mean age of 6.6 years, mean weight of 25.4 kg, and had maximum plasma epinephrine concentrations of 2289 pg/mL at 15 minutes. Mean systolic blood pressure 30 minutes after injection was significantly higher with the EpiPen than with EpiPen Jr. Transient pallor was noted in all 10 subjects after injection. Tremor and anxiety were noted in some subjects receiving EpiPen Jr and in all subjects receiving EpiPen. Some of the EpiPen recipients also experienced headache and nausea.
Although EpiPen raised systolic blood pressure significantly more than did EpiPen Jr, the higher-dose device was associated with distinctly more side effects. The small study sample size, coupled with the fact that the children receiving EpiPen Jr were significantly smaller, likely explains the failure to identify a significant difference in peak plasma epinephrine concentrations after the 2 different doses. In the absence of more dosing options in children in the 15- to 30-kg weight range, the prescribing physician must rely on certain clinical details. The EpiPen should be considered when: weight is close to 30 kg; the patient has asthma (a known poor prognostic factor in anaphylaxis); history of severe acute allergic event; and suboptimal access to emergency care. The adverse effects of epinephrine are largely unavoidable, given the narrow therapeutic index of the drug. This fact is not justification for delay in administering epinephrine, because such delay is also associated with poorer prognosis. Additional EpiPen fixed doses need to be made available for children in the 15- to 30-kg range.
The major problem we face is parental/other responsible party fear of administering the EpiPen or EpiPen Jr device, despite extensive education regarding all aspects of the clinical problem, including the treachery that comes with the “wait to see if things get worse” approach. Although it would be good if we could fine-tune EpiPen dosing better in the weight group discussed in this article, this core compliance problem will remain. Proper contingency treatment with an EpiPen of whatever dosing strength will continue to require lots of encouragement and reinforcement for parents especially.