title: Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?
abstract: BACKGROUND
  For out-of-hospital treatment of anaphylaxis, inhalation of epinephrine from a pressurized metered-dose inhaler is sometimes recommended as a noninvasive, user-friendly alternative to an epinephrine injection.
  
  
  OBJECTIVE
  To determine the feasibility of administering an adequate epinephrine dose from a metered-dose inhaler in children at risk for anaphylaxis by assessing the rate and extent of epinephrine absorption after inhalation.
  
  
  METHODS
  We performed a prospective, randomized, observer-blind, placebo-controlled, parallel-group study in 19 asymptomatic children with a history of anaphylaxis. Based on the child's weight, 10, 15, or 20 carefully supervised epinephrine or placebo inhalations were attempted. Before dosing, and at intervals from 5 to 180 minutes after dosing, we monitored plasma epinephrine concentrations, blood glucose, heart rate, blood pressure, and adverse effects.
  
  
  RESULTS
  Eleven children (mean +/- standard error of the mean: 9 +/- 1 years and 33 +/- 3 kg) in the epinephrine group were able to inhale 11 +/- 2 (range: 3-20) puffs, equivalent to 74% +/- 7% of the precalculated dose or 0.078 +/- 0.009 mg/kg. They achieved a mean peak plasma epinephrine concentration of 1822 +/- 413 (range: 230-4518) pg/mL at 32.7 +/- 6.2 minutes. Eight children (10 +/- 1 years of age and 33 +/- 5 kg) in the placebo group were able to inhale 12 +/- 2 (range: 8-20) puffs, 89% +/- 3% of the precalculated dose, and had a peak endogenous plasma epinephrine concentration of 1316 +/- 247 (range: 522-2687) pg/mL at 44.4 +/- 16.7 minutes. In the children receiving epinephrine compared with those receiving placebo, mean plasma epinephrine concentrations were not significantly higher at any time, mean blood glucose concentrations were significantly higher from 10 to 30 minutes, mean heart rate was not significantly different at any time, and mean systolic and diastolic blood pressures were not significantly increased at most times. After the inhalations of epinephrine or placebo, the children complained of bad taste and many experienced cough or dizziness. After inhaling epinephrine, 1 child developed nausea, pallor, and muscle twitching.
  
  
  CONCLUSIONS
  Despite expert coaching, because of the number of epinephrine inhalations required and the bad taste of the inhalations, most children were unable to inhale sufficient epinephrine to increase their plasma epinephrine concentrations promptly and significantly. Therefore, we urge caution in recommending epinephrine inhalation as a substitute for epinephrine injection for out-of-hospital treatment of anaphylaxis symptoms in children.
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. simons@ms.umanitoba.ca
authors.forename: F E
authors.initials: FE
authors.lastname: Simons
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: L M
authors.initials: LM
authors.lastname: Johnston
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000280:Administration, Inhalation; D000367:Age Factors; D000553:Ambulatory Care; D000707:Anaphylaxis / Q000517:prevention & control*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002648:Child; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D009330:Nebulizers and Vaporizers / Q000706:statistics & numerical data; D010919:Placebos; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D010919:Placebos; D004837:Epinephrine