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Three Part Question

For [management of anaphylaxis] is [intramuscular or subcutaneous adrenaline] most [effective]?

Clinical Scenario

A 29 year old male is brought to A&E in an ambulance after eating accidentally eating prawns at a restaurant. He is allergic to seafood and has had anaphylactic reactions in the past. His symptoms are severe, he is struggling to breathe and is hypotensive. Adrenaline is required, you wonder if a subcutaneous injection would be more effective than an intramuscular one.

Search Strategy

Medline 1946 to June Week 1 2013
EMBASE 1980 to 2013 Week 26

((exp hypersensitivity/) OR (exp anaphylaxis/) OR (anaphyla$.mp) OR (allerg$.mp) OR (acute ADJ allergic ADJ reaction)) AND ((exp epinephrine/) OR (adrenalin$.mp) OR (epipen.mp) OR(JEXT.mp) OR (auvi-Q.mp) OR (auto-injector.mp)) AND ((exp injections, subcutaneous/) OR (subcutaneou$.mp) OR (SC.mp) OR (under skin.mp)) AND ((exp injections, intramuscular/) OR (intramuscular$.mp) OR (IM.mp) OR (into muscle.mp) LIMITS English Language, Humans

Search Outcome

148 papers were found, two were relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Simons FER et al 2001 Canada	13 Healthy young men Received 6 injections over a number of visits to the study centre a combination of IM adrenaline from ampoule in the thigh IM adrenaline via an Epipen, SC adrenaline in the upper arm, IM adrenaline in the deltoid, IM saline in the upper arm and SC saline in the upper arm	Prospective, randomised, blinded, placebo-controlled 6-way crossover study	Plasma adrenaline levels before and up to 180 minutes after injection	Mean plasma adrenaline level after IM injection was significantly higher than that from SC injection. (1821±426pg/ml vs. 2877±567pg/ml) p<0.01	Small sample size Healthy individuals Deltoid results used as there was no SC injection in the thigh. Mean BMI of 36.6 (obese) – possible that IM injections may have been SC due to the thickness of subcutaneous tissue
Simons FER et al 1998 Canada	Randomised, single blind, single dose, parallel group pilot study (double blinding considered unethical due to increased number of injections for children)	17 children (4-12 years old) with a history of anaphylaxis Injected with IM adrenaline via Epipen (n=9) or SC adrenaline (n=8) Both groups were statistically similar	Mean plasma adrenaline levels	The mean plasma adrenaline levels were significantly higher after IM injection vs SC injections (2136±351pg/ml vs 1802±214pg/ml) p<0.05	Investigators were not blinded. No details on the site of the injection. Children were healthy during study, not experiencing allergic reaction.
			The mean time to achieve maximum plasma adrenaline levels	Mean time to achieve maximum plasma adrenaline concentration is significantly shorter after IM injection vs. SC (8±2 minutes vs. 34±14 minutes) p<0.05

Comment(s)

The above papers conclude that IM adrenaline is superior to SC in terms of maximum plasma concentrations and average time taken to achieve this, important as delay in administration of adrenaline (which would be exacerbated by a slow onset) has been shown to causes death. It should be noted the majority of participants in the 2001 study were obese. There has been some concern the 1.43cm needle contained with AAIs is too short to penetrate the subcutaneous tissue in obese individuals therefore it is possible the ‘IM’ doses in this study were in fact ‘SC’.

Clinical Bottom Line

Although SC and IM injections in the thigh (the preferred location for administration) have still yet to be considered, the above evidence suggests IM adrenaline should be used during anaphylaxis.

References

1. Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection J Allergy Clin Immunol 2001;108(5):871-3.
2. Simons FER, Roberts JR, Gu X, Simons KJ... Epinephrine absorption in children with a history of anaphylaxis Journal of Allergy and Clinical Immunology 1998;101(1):33-7.