Supplementary Table

Topic ReferenceComments on Quality of evidenceGrading

the paper

Epidemiology and characteristics
of anaphylaxis. / Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med.2001;161:15–21 / Review article on the prevalence of anaphylaxis in the USA to food, drugs, latex, and insect stings. The authors conclude that anaphylaxis occurs more frequently than previously thought: 3.29 to 40.9 million individuals may be at risk. / Although anaphylaxis likely is under- reported in the USA. the wide range of the prevalence estimates reveals their inherent limitations and imprecision. / N/A (epidemiological study)
Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol.2001;107:191–193 / Review of 32 deaths from food-related anaphylaxis (age range 2 - 33 years). Peanuts followed by tree nuts accounted for > 90% of the deaths. Prior history of food allergy, asthma, or delayed administration of epinephrine also noted in the majority of cases. / Small,
retrospective case series. / N/A
(epidemiological study)
AAAAI Board of Directors. Anaphylaxis in schools and other childcare settings. J Allergy Clin Immunol. 1998;102:173–176 / 1-2% of the U.S. population may be at risk for anaphylaxis. Each year, 50 deaths from insect stings and 100 deaths from food allergies are reported. In anaphylaxis, epinephrine may be administered by self or by trained caretakers. / Consensus statement based on limited literature search and expert opinion. / 1C
Lieberman P, Camargo CA, Bohlke K, et al. Epidemiology of Anaphylaxis. Ann Allergy Asthma Immunol. 2006;
97:596–602. / Anaphylaxis occurs approximately 50-2000 episodes per 100,000 persons, or lifetime prevalence of 0.05%-2.0%. / Literature review of a subject matter in which data are sparse and imprecise. / N/A
(epidemiological study)
Pumphrey R. Anaphylaxis: can we tell who is at risk of a fatal reaction?.CurrOpin Allergy Clin Immunol. 2004;4:285–290. / Review of fatal and non-fatal cases of anaphylaxis in the UK. Median time from antigen exposure to fatal collapse: food-30 minutes; drugs-5 min; stings-12 min. / Retrospective case series. / N/A
(epidemiological study)
Treatment of anaphylaxis. / Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108:871–873 / Intramuscular (IM) injection of epinephrine in the anterolateral thigh resulted in higher serum concentrations of epinephrine compared to IM injection in the deltoid or subcutaneous injection in either area. / Small, randomized, blinded study (n=13) in male volunteers. / 1B
Sheikh A, Shehata YA, Brown SGA, Simons FER. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database Systematic Rev. 2008;4:CD006312. Edited and republished online 18 April 2012. / Available evidence suggests benefit to epinephrine in the treatment of anaphylaxis. / Systematic review based on observational studies, case reports, and expert opinion. / 1C
Simons FER, Chan ES, Xiaochen Gu, Simons KJ.
Epinephrine for the out-of- hospital (first-aid) treatment of anaphylaxis in infants: Is the ampoule/syringe/needle method practical? J Allergy Clin Immunol. 2011;108: 1040-1044. / Measured how accurately and quickly parents drew up an infant dose of epinephrine using a needle with syringe. Parents took 90 seconds longer than MDs to give epinephrine, but gave an accurate dose. / Small, prospective, controlled simulation study (n=18). / 1B
Stecher D, Bulloch B, Sales J, Schaefer, Keahey, L. Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly?Pediatrics. 2009;124:65-70 / Using ultrasound measurements, the authors determined that the needle length in standard epinephrine auto- injectors may not reach muscle in 12 - 30% of children. / Surrogate marker of potential but indeterminate clinical relevance. / 2C
Bhalla MC, Gable BD, Frey JA, et al. Predictors of epinephrine autoinjector needle length inadequacy. American Journal of Emergency Medicine. 2013; 31:1671-1676 / Using ultrasound measurements,, the authors determined that the needle length in standard epinephrine auto- injectors may not reach muscle in 31% of adults, particularly in female or obese subjects. / Surrogate marker of potential but indeterminate clinical relevance. / 2C
Lammers R, Willoughby- Byrwa M, Fales W. Medication errors in prehospital management of simulated pediatric anaphylaxis. Prehospital Emergency Care. 2014; 18:295-304. / EMS crews correctly administered epinephrine using an ampoule and syringe with needle 46% of the time. Study recommended
use of a standard auto-injector or more frequent training to improve accuracy. / Prospective trial based on a simulated case (n=62). / 1B
Biphasic reactions in anaphylaxis / Rudders SA, Banerji A, Corel B, et al. Multicenter study of repeat epinephrine treatments for food-related anaphylaxis. Pediatrics. 2010;125:711-718 / Approximately 12% of children may require a second dose of epinephrine to treat food-related anaphylaxis. / Retrospective chart review of 330 children . / 1B
Grunau BE, Li J, Yi TW et al.Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients With Allergic Reactions or Anaphylaxis. Ann Emerg Med. 2013 November 13. Epub ahead of print. PMID 24239340. / Clinically important biphasic reactions occurred in 0.40% of patients with anaphylaxis and 0.13% of patients with allergic reaction. / Retrospective review of ED adult patients with allergic
reaction (n=2323) and anaphylaxis (n=496). / 1B
Douglas DM, Sukenick E, Andrade WP, Brown JS. Biphasic systemic anaphylaxis: An inpatient and outpatient study. J Allergy Clin Immunol. 1994; 93:977-85. / Biphasic reactions occurred in 7% of hospital patients and 5% of clinic patients with anaphylaxis. / Retrospective review of 59 hospital patients admitted for anaphylaxis and 35 clinic patients treated for anaphylaxis after allergen immunotherapy injections. / 1C
Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol. 2007; 98:64-69. / Anaphylaxis recurred in 19.4% of patients an average of 10 hours after initial treatment. Undertreatment with epinephrine or steroids may have contributed to recurrence. / Prospective, observational study with follow up in 77% of patients. / 1B