Adrenaline administration route
It is unclear whether different adrenaline administration routes affect
outcomes because the certainty of evidence is very low.
We identified two randomised trials and two non-randomised trials about
adrenaline inhalation as the primary route of administration; three in
adults and one in children. Most studies found that inhalation did not
deliver a therapeutically appropriate dose of adrenaline or reduce
adverse effects compared to intramuscular or subcutaneous injection or
placebo (very low certainty, supplement S5c).11Breuer C, Wachall
B, Gerbeth K, Abdel-Tawab M, Fuhr U. Pharmacokinetics and
pharmacodynamics of moist inhalation epinephrine using a mobile
inhaler. Eur J Clin Pharmacol 2013;69(6):1303-1310.,22Foucard
T, Cederblad F, Dannaeus A, Swenne I, Niklasson F. Anaphylaxis in
severe food allergy. Adrenaline injection is safer than inhalation.
Lakartidningen 1997;94(16):1478, 1483.,33Heilborn
H, Hjemdahl P, Daleskog M, Adamsson U. Comparison of subcutaneous
injection and high-dose inhalation of epinephrine–implications for
self-treatment to prevent anaphylaxis. J Allergy Clin Immunol
1986;78(6):1174-1179.,44Simons FE, Gu X,
Johnston LM, Simons KJ. Can epinephrine inhalations be substituted for
epinephrine injection in children at risk for systemic anaphylaxis?
Pediatrics 2000;106(5):1040-1044.
One consecutive case series in children and adults found that
intravenous bolus administration was associated with a 13% increase in
the incidence of adrenaline overdose (OR 61.3, 95% CI 7.5 to infinity)
and an 8% increase in the incidence of cardiovascular events compared
with intramuscular administration (OR 7.5, 95% CI, 1.6 to 35.3, very
low certainty, supplement S5d and Table 3).55Campbell RL,
Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, Hess
EP. Epinephrine in anaphylaxis: higher risk of cardiovascular
complications and overdose after administration of intravenous bolus
epinephrine compared with intramuscular epinephrine. J Allergy Clin
Immunol Pract 2015;3(1):76-80.
Two trials compared intramuscular versus subcutaneous injection of
adrenaline in children and young adults. Intramuscular adrenaline was
associated with an absolute increase of mean plasma adrenaline
concentration (very low certainty, supplement S5e).66Simons FE,
Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular
versus subcutaneous injection. J Allergy Clin Immunol
2001;108(5):871-873.,77Simons FE, Roberts
JR, Gu X, Simons KJ. Epinephrine absorption in children with a history
of anaphylaxis. J Allergy Clin Immunol 1998;101(1 Pt 1):33-37.
However these studies may be confounded by using different injection
sites (thigh versus arm), in addition to different depth of injection.
Adrenaline autoinjectors are not readily available everywhere so
alternatives have been tested. One trial with caregivers of children at
risk of anaphylaxis tested an adrenaline autoinjector versus a
pre-filled syringe. 61% more people using a prefilled syringe
administered adrenaline without errors compared to those using an
autoinjector (OR 4.07, 95% CI 1.29 to 12.86, low certainty, supplement
S5f).88Suwan P, Praphaiphin P, Chatchatee P. Randomized
comparison of caregivers’ ability to use epinephrine autoinjectors and
prefilled syringes for anaphylaxis. Asian Pac J Allergy Immunol
2018;36(4):248-256.
In a non-randomised trial, health professionals tested an autoinjector
or a syringe (not pre-filled). Using an autoinjector reduced the time to
administration by an average of 70 seconds compared to a syringe and
resulted in fewer administration errors (statistically significant,
confidence intervals not reported, very low certainty, supplement
S5g).99Asch D, Pfeifer KE, Arango J, Staib L, Cavallo J, Kirsch
JD, Arici M, Pahade J. Benefit of Epinephrine Autoinjector for
Treatment of Contrast Reactions: Comparison of Errors, Administration
Times, and Provider Preferences. AJR Am J Roentgenol
2017;209(2):W363-W369.