Keeping 2 doses of epinephrine on hand is recommended for children with life-threatening food allergies, according to a study published online March 22 in Pediatrics.

Approximately 3 million children in the United States have food allergies, and that number is growing. Food allergies are the chief cause of anaphylaxis, a sometimes-fatal allergic response, which progresses quickly to constrict the airway, irritate the skin and intestines, and/or affect heart rhythm. It is treated with an injection of epinephrine (adrenaline), which stimulates the heart, and elevates blood pressure, metabolic rate, and blood glucose concentration.

A number of small studies recommend that children who have experienced anaphylaxis brought on by food allergies should carry several doses of epinephrine. The suggestion brings up issues of cost and logistics.

“Therefore, we sought to more accurately define the likelihood of receiving dose of epinephrine for food-related anaphylaxis and to characterize the children for whom this was medically necessary,” write Carlos A. Camargo Jr, MD, DrPH, from the Department of Emergency Medicine, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, and colleagues.

Using charts from Massachusetts General and Children’s hospitals, investigators reviewed 605 cases of 1255 patients whose mean age was 5.8 years. A total of 62% were boys. All subjects arrived at the emergency department (ED) between 2001 and 2006 with allergic reactions related to foods, typically nuts and milk. The investigators measured acute reactions using the International Classification of Diseases, Ninth Revision, Clinical Modification, criteria.

An allergic reaction to 2 or more organ systems or the presence of hypotension (< 70 mm Hg + [age x 2 years] for children <10 years old, and < 90 mm Hg for children 10 – 18 years old) after exposure to an allergy-causing food was used to define anaphylaxis. Mean ± standard error and a 95% confidence interval (CI) were used to derive data. Statistical significance was achieved with a 2-sided P value of less than .05 in multivariable analysis, with use of unweighted numbers of visits to determine risk factors for a second dose of epinephrine.

Of Those Needing Epinephrine, 12% Required Second Dose

The results show that more than half (52%; 95% CI, 48% – 57%) of the subjects met the criteria for anaphylaxis stemming from foods, among other findings:

  • Before their arrival at the ED, 31% of patients with anaphylaxis had received 1 dose of epinephrine, and 3% had received more than 1 dose.
  • Once in the ED, 20% of those with anaphylaxis were treated with epinephrine; the others received antihistamines (59%) or corticosteroids (56%).
  • During the entirety of their allergic episode, 44% of participants with anaphylaxis received epinephrine.
  • Among those receiving epinephrine, 12% (95% CI, 9% – 14%) required more than 1 dose.

“This finding supports the recommendation that children at risk for food-related anaphylaxis carry 2 doses of self-injectable epinephrine,” the study authors write.

Older age and having been transferred from another hospital were risk factors for a subsequent dose.

The study authors noted 3 limitations. First, the use of medical charts may have resulted in the inclusion of inaccurate or incomplete data. Second, the number of patients receiving epinephrine may have been overestimated because of the exclusive focus on ED cases. Finally, the hospital EDs in the study are in an academic, urban setting, possibly resulting in data that may not be nationally representative.

Advantages of Having a Second Dose

When asked for independent comment about the study, Raymond Slavin, MD, professor of allergy and immunology, Saint Louis University, St. Louis, Missouri told Medscape Pediatrics, “The study documents in children what has long been understood about adults and food allergies.”

“It’s been known for several years that frequently a second or delayed reaction may occur after the patient has had a severe reaction,” Dr. Slavin said.

Keeping more than 1 auto-injector on hand is necessary even if a child does not have a secondary reaction, according to Dr. Slavin. “There are always advantages to having an extra one. If it’s outdated, or if the first one wasn’t given properly, a backup is a very good idea,” he said.

Auto-injectors expire after 1 year. Although most insurance policies include coverage for epinephrine, many pay for only a limited number of the injection devices. Even with insurance, some families may have to cover the full purchase price for additional auto-injectors, which can run several hundred dollars for a twin pack. The investigators recommend that schools help to ensure all children have access to more than 1 dose.

“Given that children often require medications in multiple locations, consideration should be given to cost-saving approaches such as having unassigned second doses available at schools and day cares,” the study authors write. “Additional study is warranted to evaluate the long-term outcomes of children who experience an episode of food-related anaphylaxis and methods to improve and standardize their care.”

The study was supported by the National Institutes of Health and Dey Laboratories. Dr. Camargo has consulted for Dey and is the lead investigator of another study supported by Dey. The study authors have disclosed no other relevant financial relationships.

Dr. Slavin has disclosed no relevant financial relationships.

Pediatrics. Published online March 22, 2010.

Clinical Context

The prevalence of food allergies in developed countries is currently nearly 6% and appears to be increasing. Recent studies also suggest a dramatic increase in the incidence of anaphylaxis, with food allergy shown to be the leading cause of anaphylaxis in children.

Current practice guidelines recommend that all patients suspected of having an episode of food-related anaphylaxis be referred to an allergist, counseled to avoid the suspected food trigger, and prescribed self-injectable epinephrine. Prompt administration of epinephrine is the primary treatment of food-related anaphylaxis. It is recommended that children with a history of food-related anaphylaxis carry multiple doses of self-injectable epinephrine, although evidence supporting this practice is limited.

Study Highlights

  • The goal of this multicenter study was to determine the frequency of receiving more than 1 dose of epinephrine in children who present to the ED with food-related anaphylaxis.
  • The investigators performed a medical chart review of all children who presented to the ED at Boston hospitals between January 1, 2001, and December 31, 2006, for food-related acute allergic reactions.
  • Data were extracted regarding food triggers, clinical features, and emergency treatments.
  • The investigators reviewed 605 cases, which through random sampling and appropriate weighting represented a study cohort of 1255 patients.
  • Median age was 5.8 years (95% CI, 5.3 – 6.3 years), and 62% were boys.
  • Food triggers for the allergic reactions included peanuts in 23%, tree nuts in 18%, and milk in 15%.
  • Home was the most common setting for exposure, but approximately one third of cases occurred in other locations.
  • Diagnostic criteria for food-related anaphylaxis were met by 52% of children (95% CI, 48% – 57%).
  • Children with food-related anaphylaxis were more likely to have a history of atopic disease, especially asthma.
  • Nearly half (44%) of the children with anaphylaxis were known to be allergic to the food that triggered this reaction.
  • Before arrival to the ED, 31% of those with anaphylaxis received 1 dose of epinephrine, and 3% received more than 1 dose.
  • Among patients with anaphylaxis who received more than 1 dose of epinephrine, 69% were known to be allergic to the implicated food.
  • Treatments administered in the ED included antihistamines in 59% of patients with anaphylaxis, corticosteroids in 56%, and epinephrine in 20%, despite the lack of evidence for the usefulness of antihistamines and corticosteroids as first-line treatments of anaphylaxis.
  • Despite current guidelines recommending intramuscular administration, epinephrine was most frequently administered subcutaneously in the ED.
  • During the course of their allergic reaction, 44% of patients with food-related anaphylaxis received epinephrine.
  • Among this subset of patients, 12% received more than 1 dose.
  • Risk factors for subsequent epinephrine use included older age and transfer from an outside hospital.
  • Most of the children (88%) were discharged from the ED.
  • Self-injectable epinephrine was prescribed to 43% of children on discharge from the ED.
  • Only 22% were referred to an allergist on discharge from the ED.
  • Only 13% of cases that met the criteria for anaphylaxis had an ED discharge diagnosis that included the term anaphylaxis.
  • The investigators concluded that among children with food-related anaphylaxis who received epinephrine, 12% received a second dose, supporting the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine.
  • Limitations of this study include reliance on medical chart documentation, possible overestimation of the percentage of patients receiving epinephrine because the review was limited to the ED, and lack of generalizability because the 2 hospitals evaluated were in an urban, academic setting.

Clinical Implications

  • Among children presenting to the ED with food-related anaphylaxis who received epinephrine, 12% received a second dose. This finding supports the recommendation that children at risk for food-related anaphylaxis should carry 2 doses of self-injectable epinephrine.
  • Food-related anaphylaxis continues to be underrecognized and inadequately treated in the ED setting. Despite the lack of evidence for the usefulness of antihistamines and corticosteroids as first-line treatments of anaphylaxis, these were administered in the ED more often than epinephrine.

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