Type of study and grade of evidence

Type of study and grade of evidence

Reference Type of study Grade of evidence

Yocum et al³ Retrospective population based cohort study C

Stewart et al⁴ Retrospective analysis of emergency admissions over two separate three month periods C

Klein et al⁵ Retrospective analysis of emergency admissions over four month period C

Neugut et al⁶ Review of literature to obtain prevalence estimates of anaphylaxis in United States C

Johnston et al⁷ Case reports C

Pumphrey⁸ Review of death certificate register between 1992 and 1998 for episodes of fatal anaphylaxis and subsequent review of these patients management C

Bautista et al^w1 Randomised placebo controlled trial assessing haemodynamic response to subcuataneous, intramuscular, and intravenous adrenaline (epinephrine) in canine anaphylactic shock model B

Horowitz et al^w2 Case report C

Davis et al^w3 Case report C

Simons¹² Prospective, randomised, blinded, parallel group study in 17 children with history of anaphylaxis. B

Simons et al¹³ Prospective randomised blinded placebo controlled six way cross over study of intramuscular versus subcutaneous epinephrine in young men B

Heliborn et al^w6 Comparison of systemic adrenaline absorption in 12 healthy volunteers after inhaled or subcutaneous administration C

Dahlof et al^w4 Comparison of systemic adrenaline absorption in eight healthy volunteers after inhaled, subcutaneous, and eye drop administration C

Moneret Vautrin et al¹⁶ Case report C

Sampson et al¹⁷ Retrospective analysis of fatal and near fatal anaphylactic reactions in children and adolescents over 14 month period C

Soreide et al¹⁸ Retrospective review of 27 anaphylactic reactions treated by anaesthesiologist staffed ambulance helicopters during five year period C

Macdougall et al¹⁹ Retrospective analysis of paediatric fatalities 1990-98 using death certificate register, and prospective analysis of severe and fatal reactions 1998-2000 using British Paediatric Surveillance System C

Zimmerman et al²⁰ Analysis of 96 consecutive patients who were skin prick test positive to peanut attending one year follow up C

Pumphrey^w8 Retrospective survey of 1130 patients attending allergy clinic C

Goldberg et al²³ Analysis of attitudes of 96 patients receiving immunotherapy towards using, and ability to use, Epipen (ALK-Abelló) device C

Gold et al²⁵ Retrospective survey of children with history of anaphylaxis who had been prescribed Epipen device C

Simons et al^w9 Prospective, randomised cross over study of adrenaline bioavailability in out-dated Epipens by injection into rabbits, spectrophotometry, and high performance liquid chromatography B

Box

Box 1: Grades for levels of evidence

Grade A: based on a meta-analysis or at least one randomised control trial

Grade B: based on at least one well designed, but not necessarily controlled, study, including case control and comparative studies

Grade C: based on expert reports or opinions

Web references

w1 Bautista E, Simons FE, Simons KJ, Becker AB, Duke K, Tillett M, et al. Epinephrine fails to hasten the haemodynamic recovery in fully developed canine anaphylactic shock. Intern Arch Allergy Immunol 2002;128:151-64.

w2 Horowitz BZ, Jadallah S, Derlet RW. Fatal intracranial bleeding associated with prehospital use of epinephrine. Ann Emerg Med 1996;28:725-7.

w3 Davis CO, Wax PM. Prehospital epinephrine overdose in a child resulting in ventricular dysrhythmias and myocardial ischaemia. Paediatr Emerg Care 1999;15(2):116-8.

w4 Dahlof C, Mellstrand T, Svedmyr N. Systemic absorption of adrenaline after aerosol, eye-drop and subcutaneous administration to healthy volunteers. Allergy 1987;42:215-21.

w5 Plomley RF. Inhaled adrenaline in the treatment of anaphylaxis. Med J Aust 1988;149:564.

w6 Heliborn H, Hjemdahl P, Daleskog M, Adamsson U. Comparison of subcutaneous injection and high dose inhalation epinephrine—implications for self-treatment to prevent anaphylaxis. J Emerg Med 1991;10:693-8.

w7 Adrenaline for anaphylaxis. Drug Ther Bull 1994;32(3):19-21.

w8 Pumphrey R. How helpful is adrenaline self treatment? Immunology 1999;98(suppl 1):145.

w9 Simons FE, Gu X, Simons KJ. Outdated Epipen and Epipen Junior autoinjectors: past their prime? J Allergy Clin Immunol 2000;105:1025-30.

Reference	Type of study	Grade of evidence
Yocum et al³	Retrospective population based cohort study	C
Stewart et al⁴	Retrospective analysis of emergency admissions over two separate three month periods	C
Klein et al⁵	Retrospective analysis of emergency admissions over four month period	C
Neugut et al⁶	Review of literature to obtain prevalence estimates of anaphylaxis in United States	C
Johnston et al⁷	Case reports	C
Pumphrey⁸	Review of death certificate register between 1992 and 1998 for episodes of fatal anaphylaxis and subsequent review of these patients management	C
Bautista et al^w1	Randomised placebo controlled trial assessing haemodynamic response to subcuataneous, intramuscular, and intravenous adrenaline (epinephrine) in canine anaphylactic shock model	B
Horowitz et al^w2	Case report	C
Davis et al^w3	Case report	C
Simons¹²	Prospective, randomised, blinded, parallel group study in 17 children with history of anaphylaxis.	B
Simons et al¹³	Prospective randomised blinded placebo controlled six way cross over study of intramuscular versus subcutaneous epinephrine in young men	B
Heliborn et al^w6	Comparison of systemic adrenaline absorption in 12 healthy volunteers after inhaled or subcutaneous administration	C
Dahlof et al^w4	Comparison of systemic adrenaline absorption in eight healthy volunteers after inhaled, subcutaneous, and eye drop administration	C
Moneret Vautrin et al¹⁶	Case report	C
Sampson et al¹⁷	Retrospective analysis of fatal and near fatal anaphylactic reactions in children and adolescents over 14 month period	C
Soreide et al¹⁸	Retrospective review of 27 anaphylactic reactions treated by anaesthesiologist staffed ambulance helicopters during five year period	C
Macdougall et al¹⁹	Retrospective analysis of paediatric fatalities 1990-98 using death certificate register, and prospective analysis of severe and fatal reactions 1998-2000 using British Paediatric Surveillance System	C
Zimmerman et al²⁰	Analysis of 96 consecutive patients who were skin prick test positive to peanut attending one year follow up	C
Pumphrey^w8	Retrospective survey of 1130 patients attending allergy clinic	C
Goldberg et al²³	Analysis of attitudes of 96 patients receiving immunotherapy towards using, and ability to use, Epipen (ALK-Abelló) device	C
Gold et al²⁵	Retrospective survey of children with history of anaphylaxis who had been prescribed Epipen device	C
Simons et al^w9	Prospective, randomised cross over study of adrenaline bioavailability in out-dated Epipens by injection into rabbits, spectrophotometry, and high performance liquid chromatography	B