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.