Epinephrine absorption in children with a history of anaphylaxis,☆☆,,★★

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Abstract

Background: Prompt injection of epinephrine is the cornerstone of systemic anaphylaxis treatment. The rate of epinephrine absorption has not been reported previously in allergic children. Objective: Our objective was to study the clinical pharmacology of epinephrine in this population. Methods: We performed a prospective, randomized, blinded, parallel-group study in 17 children with a history of anaphylaxis to food, Hymenoptera venom, or other substances. We injected 0.01 ml/kg epinephrine solution (maximum 0.3 ml [0.3 mg]) subcutaneously, or 0.3 mg epinephrine intramuscularly from an autoinjector. Plasma epinephrine concentrations, heart rate, blood pressure, and adverse effects were monitored. Results: In nine children who received epinephrine subcutaneously, the mean maximum plasma epinephrine concentration (± SEM) was 1802 ± 214 pg/ml, achieved at a mean time of 34 ± 14 minutes (range, 5 to 120 minutes). Only two of the nine children achieved maximum plasma concentrations by 5 minutes. In eight children who received epinephrine intramuscularly, the mean maximum plasma concentration was 2136 ± 351 pg/ml, achieved at a mean time of 8 ± 2 minutes, which was significantly faster than the mean time at which maximum plasma concentrations were achieved after subcutaneous epinephrine injection (p < 0.05). Six of the eight children achieved maximum plasma concentrations by 5 minutes. The terminal elimination half-life was 43 ± 15 minutes. No serious adverse effects were noted in any child. Conclusions: In children, recommendations for subcutaneous epinephrine injection are based on anecdotal experience, and should be reevaluated in view of our finding of delayed epinephrine absorption when this route is used. This delay might have important clinical implications during an episode of systemic anaphylaxis. The intramuscular route of injection is preferable. (J Allergy Clin Immunol 1998;101:33-7.)

Section snippets

METHODS

We tested this hypothesis in a randomized, single-blind, single-dose, parallel-group pilot study in 17 children who received either a subcutaneous injection of 0.01 ml/kg epinephrine hydrochloride solution (maximum, 0.3 ml [0.3 mg]) or an intramuscular injection of 0.3 ml (0.3 mg) with the EpiPen Auto-Injector (Allerex Laboratory, Ltd., Kanata, Ontario, Canada).

The study was approved by the University of Manitoba Faculty Committee on the Use of Human Subjects in Research. Before entry into the

RESULTS

All the children participating in this study had a history of systemic anaphylaxis. Each child had an EpiPen available “around-the-clock” in case inadvertent contact with the allergen to which he or she was sensitive triggered another episode of anaphylaxis. The demographics of the two groups of children were similar (Table I).

. Demographic data

Empty CellEpinephrine solution (subcutaneous)EpiPen Auto-injector (intramuscular)
No. of children in group98
Age (mean ± SEM [range])8 ± 1 yr (4-12)8 ± 1 yr (7-11)

DISCUSSION

The epinephrine doses and routes of administration selected for testing were based on current published recommendations.3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Ideally, the study would have been conducted in children during an actual episode of systemic anaphylaxis. As frequent timed blood samples are extremely difficult to obtain prospectively during a medical emergency when all efforts are focused on preservation of life, we opted instead to conduct it in highly allergic children at risk for

Acknowledgements

We thank Mrs. Diane Dilay, RN, and Mrs. Cathy Gillespie, RN, for their expertise.

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From athe Section of Allergy and Clinical Immunology, Department of Pediatrics and Child Health, Faculty of Medicine and bthe Division of Pharmaceutical Sciences, Faculty of Pharmacy, University of Manitoba, Winnipeg.

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Supported by the Children's Hospital Research Foundation.

Reprint requests: F. Estelle R. Simons, MD, FRCPC, Children's Hospital of Winnipeg, 820 Sherbrook Street, Winnipeg, Manitoba, Canada, R3A 1R9.

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